Immune Modulation by Antigenic Peptides and Antigenic Peptide Conjugates for Treatment of Multiple Sclerosis

Main Article Content

Rucha Mahadik Paul Kiptoo Thomas Tolbert Teruna J Siahaan

Abstract

The immune system defends our body by fighting infection from pathogens utilizing both the innate and adaptive immune responses. The innate immune response is generated rapidly as the first line of defense. It is followed by the adaptive immune response that selectively targets infected cells. The adaptive immune response is generated more slowly, but selectively, by targeting a wide range of foreign particles (i.e., viruses or bacteria) or molecules that enter the body, known as antigens. Autoimmune diseases are the results of immune system glitches, where the body’s adaptive system recognizes self-antigens as foreign. Thus, the host immune system attacks the self-tissues or organs with a high level of inflammation and causes debilitation in patients. Many current treatments for autoimmune diseases (i.e., multiple sclerosis (MS), rheumatoid arthritis (RA)) have been effective but lead to adverse side effects due to general immune system suppression, which makes patients vulnerable to opportunistic infections. To counter these negative effects, many different avenues of antigen specific treatments are being developed to selectively target the autoreactive immune cells for a specific self-antigen or set of self-antigens while not compromising the general immune system. These approaches include soluble antigenic peptides, bifunctional peptide inhibitors (BPI) including IDAC and Fc-BPI, polymer conjugates, and peptide-drug conjugates. Here, various antigen-specific methods of potential treatments, their efficacy, and limitations will be discussed along with the potential mechanisms of action.

Article Details

How to Cite
MAHADIK, Rucha et al. Immune Modulation by Antigenic Peptides and Antigenic Peptide Conjugates for Treatment of Multiple Sclerosis. Medical Research Archives, [S.l.], v. 10, n. 5, june 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2804>. Date accessed: 25 june 2022. doi: https://doi.org/10.18103/mra.v10i5.2804.
Section
Review Articles

References

1. Chaplin, D. D. 1. Overview of the immune response. J Allergy Clin Immunol 2003, 111, S442-59. doi: 10.1067/mai.2003.125.
2. McNeela, E. A.; Mills, K. H. Manipulating the immune system: humoral versus cell-mediated immunity. Adv Drug Deliv Rev 2001, 51, 43-54. doi: 10.1016/s0169-409x(01)00169-7.
3. Janeway, C. A.; Travers, P.; Walport, M., The Humoral Immune Response. In Immunobiology: The Immune System in Health and Disease, Garland Science: New York, 2001.
4. Hirsch, D. L.; Ponda, P. Antigen-based immunotherapy for autoimmune disease: current status. Immunotargets Ther 2015, 4, 1-11. PMC: PMC4918244. doi: 10.2147/ITT.S49656.
5. Kammona, O.; Kiparissides, C. Recent Advances in Antigen-Specific Immunotherapies for the Treatment of Multiple Sclerosis. Brain Sci 2020, 10, 6. PMC: PMC7348736. doi: 10.3390/brainsci10060333.
6. Manikwar, P.; Kiptoo, P.; Badawi, A. H.; Buyuktimkin, B.; Siahaan, T. J. Antigen-specific blocking of CD4-specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Med Res Rev 2012, 32, 727-64. PMC: PMC4441537. doi: 10.1002/med.20243.
7. White, D. R.; Khedri, Z.; Kiptoo, P.; Siahaan, T. J.; Tolbert, T. J. Synthesis of a Bifunctional Peptide Inhibitor-IgG1 Fc Fusion That Suppresses Experimental Autoimmune Encephalomyelitis. Bioconjug Chem 2017, 28, 1867-1877. PMC: PMC5659714. doi: 10.1021/acs.bioconjchem.7b00175.
8. Acuto, O.; Cantrell, D. T cell activation and the cytoskeleton. Annu Rev Immunol 2000, 18, 165-84. doi: 10.1146/annurev.immunol.18.1.165.
9. Paul, W. E.; Seder, R. A. Lymphocyte responses and cytokines. Cell 1994, 76, 241-51. doi: 10.1016/0092-8674(94)90332-8.
10. Grakoui, A.; Bromley, S. K.; Sumen, C.; Davis, M. M.; Shaw, A. S.; Allen, P. M.; Dustin, M. L. The immunological synapse: a molecular machine controlling T cell activation. Science 1999, 285, 221-7. doi: 10.1126/science.285.5425.221.
11. Monks, C. R.; Freiberg, B. A.; Kupfer, H.; Sciaky, N.; Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998, 395, 82-6. doi: 10.1038/25764.
12. Lanzavecchia, A.; Sallusto, F. From synapses to immunological memory: the role of sustained T cell stimulation. Curr Opin Immunol 2000, 12, 92-8. doi: 10.1016/s0952-7915(99)00056-4.
13. Danese, S.; Sans, M.; Fiocchi, C. The CD40/CD40L costimulatory pathway in inflammatory bowel disease. Gut 2004, 53, 1035-43. PMC: PMC1774101. doi: 10.1136/gut.2003.026278.
14. Chen, L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004, 4, 336-47. doi: 10.1038/nri1349.
15. Poirier, N.; Blancho, G.; Vanhove, B. A more selective costimulatory blockade of the CD28-B7 pathway. Transpl Int 2011, 24, 2-11. doi: 10.1111/j.1432-2277.2010.01176.x.
16. Tseng, S. Y.; Dustin, M. L. T-cell activation: a multidimensional signaling network. Curr Opin Cell Biol 2002, 14, 575-80. doi: 10.1016/s0955-0674(02)00370-8.
17. Delon, J.; Germain, R. N. Information transfer at the immunological synapse. Curr Biol 2000, 10, R923-33. doi: 10.1016/s0960-9822(00)00870-8.
18. Gimmi, C. D.; Freeman, G. J.; Gribben, J. G.; Gray, G.; Nadler, L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A 1993, 90, 6586-90. PMC: PMC46977. doi: 10.1073/pnas.90.14.6586.
19. Gimmi, C. D.; Freeman, G. J.; Gribben, J. G.; Sugita, K.; Freedman, A. S.; Morimoto, C.; Nadler, L. M. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A 1991, 88, 6575-9. PMC: PMC52129. doi: 10.1073/pnas.88.15.6575.
20. Linsley, P. S.; Wallace, P. M.; Johnson, J.; Gibson, M. G.; Greene, J. L.; Ledbetter, J. A.; Singh, C.; Tepper, M. A. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 1992, 257, 792-5. doi: 10.1126/science.1496399.
21. Ortler, S.; Leder, C.; Mittelbronn, M.; Zozulya, A. L.; Knolle, P. A.; Chen, L.; Kroner, A.; Wiendl, H. B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage: implications for the lesion pathogenesis of multiple sclerosis. Eur J Immunol 2008, 38, 1734-44. doi: 10.1002/eji.200738071.
22. Jenkins, M. K.; Taylor, P. S.; Norton, S. D.; Urdahl, K. B. CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells. J Immunol 1991, 147, 2461-6.
23. Salomon, B.; Bluestone, J. A. LFA-1 interaction with ICAM-1 and ICAM-2 regulates Th2 cytokine production. J Immunol 1998, 161, 5138-42.
24. Salomon, B.; Bluestone, J. A. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 2001, 19, 225-52. doi: 10.1146/annurev.immunol.19.1.225.
25. Luksch, C. R.; Winqvist, O.; Ozaki, M. E.; Karlsson, L.; Jackson, M. R.; Peterson, P. A.; Webb, S. R. Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells. Proc Natl Acad Sci U S A 1999, 96, (6), 3023-8. PMC: PMC15888. doi: 10.1073/pnas.96.6.3023.
26. Rengarajan, J.; Szabo, S. J.; Glimcher, L. H. Transcriptional regulation of Th1/Th2 polarization. Immunol Today 2000, 21, 479-83. doi: 10.1016/s0167-5699(00)01712-6.
27. Probst, H. C.; McCoy, K.; Okazaki, T.; Honjo, T.; van den Broek, M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol 2005, 6, 280-6. doi: 10.1038/ni1165.
28. Ghasemi, N.; Razavi, S.; Nikzad, E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J 2017, 19, 1-10. PMC: PMC5241505. doi: 10.22074/cellj.2016.4867.
29. Constantinescu, C. S.; Farooqi, N.; O'Brien, K.; Gran, B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011, 164, 1079-106. PMC: PMC3229753. doi: 10.1111/j.1476-5381.2011.01302.x.
30. Damsker, J. M.; Hansen, A. M.; Caspi, R. R. Th1 and Th17 cells: adversaries and collaborators. Ann N Y Acad Sci 2010, 1183, 211-21. PMC: PMC2914500. doi: 10.1111/j.1749-6632.2009.05133.x.
31. Haak, S.; Gyulveszi, G.; Becher, B. Th17 cells in autoimmune disease: changing the verdict. Immunotherapy 2009, 1, (2), 199-203. doi: 10.2217/1750743X.1.2.199.
32. Kiptoo, P.; Buyuktimkin, B.; Badawi, A. H.; Stewart, J.; Ridwan, R.; Siahaan, T. J. Controlling immune response and demyelination using highly potent bifunctional peptide inhibitors in the suppression of experimental autoimmune encephalomyelitis. Clin Exp Immunol 2013, 172, 23-36. PMC: PMC3719928. doi: 10.1111/cei.12029.
33. Stern, J. N.; Illes, Z.; Reddy, J.; Keskin, D. B.; Sheu, E.; Fridkis-Hareli, M.; Nishimura, H.; Brosnan, C. F.; Santambrogio, L.; Kuchroo, V. K.; Strominger, J. L. Amelioration of proteolipid protein 139-151-induced encephalomyelitis in SJL mice by modified amino acid copolymers and their mechanisms. Proc Natl Acad Sci U S A 2004, 101, 11743-8. PMC: PMC511046. doi: 10.1073/pnas.0403832101.
34. Badawi, A. H.; Siahaan, T. J. Immune modulating peptides for the treatment and suppression of multiple sclerosis. Clin Immunol 2012, 144, 127-38. PMC: PMC3415220. doi: 10.1016/j.clim.2012.05.010.
35. Brandstadter, R.; Katz Sand, I. The use of natalizumab for multiple sclerosis. Neuropsychiatr Dis Treat 2017, 13, 1691-1702. PMC: PMC5499927. doi: 10.2147/NDT.S114636.
36. Buyuktimkin, B.; Kiptoo, P.; Siahaan, T. J. Bifunctional Peptide Inhibitors Suppress Interleukin-6 Proliferation and Ameliorates Murine Collagen-Induced Arthritis. J Clin Cell Immunol 2014, 5, (6). PMC: PMC4524745. doi: 10.4172/2155-9899.1000273.
37. Muraoka, S.; Yamada, Z.; Kawazoe, M.; Hirose, W.; Kono, H.; Yasuda, S.; Komano, Y.; Kawano, H.; Hidaka, T.; Nakashima, S.; Kasama, T.; Teramoto, T.; Nanki, T.; group, A.-A. s. Abatacept is Efficacious in the Treatment of Older Patients with csDMARD-Refractory Rheumatoid Arthritis: A Prospective, Multicenter, Observational Study. Rheumatol Ther 2021, 8, 1585-1601. PMC: PMC8572263. doi: 10.1007/s40744-021-00356-2.
38. Roep, B. O.; Solvason, N.; Gottlieb, P. A.; Abreu, J. R. F.; Harrison, L. C.; Eisenbarth, G. S.; Yu, L.; Leviten, M.; Hagopian, W. A.; Buse, J. B.; von Herrath, M.; Quan, J.; King, R. S.; Robinson, W. H.; Utz, P. J.; Garren, H.; Investigators, B. H. T.; Steinman, L. Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8(+) T cells in type 1 diabetes. Sci Transl Med 2013, 5, 191ra82. PMC: PMC4516024. doi: 10.1126/scitranslmed.3006103.
39. Yoon, J. W.; Yoon, C. S.; Lim, H. W.; Huang, Q. Q.; Kang, Y.; Pyun, K. H.; Hirasawa, K.; Sherwin, R. S.; Jun, H. S. Control of autoimmune diabetes in NOD mice by GAD expression or suppression in beta cells. Science 1999, 284, 1183-7. doi: 10.1126/science.284.5417.1183.
40. Barouch, F. C.; Miyamoto, K.; Allport, J. R.; Fujita, K.; Bursell, S. E.; Aiello, L. P.; Luscinskas, F. W.; Adamis, A. P. Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes. Invest Ophthalmol Vis Sci 2000, 41, 1153-8.
41. Moriyama, H.; Yokono, K.; Amano, K.; Nagata, M.; Hasegawa, Y.; Okamoto, N.; Tsukamoto, K.; Miki, M.; Yoneda, R.; Yagi, N.; Tominaga, Y.; Kikutani, H.; Hioki, K.; Okumura, K.; Yagita, H.; Kasuga, M. Induction of tolerance in murine autoimmune diabetes by transient blockade of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 pathway. J Immunol 1996, 157, 3737-43.
42. Gottlieb, A. B.; Krueger, J. G.; Wittkowski, K.; Dedrick, R.; Walicke, P. A.; Garovoy, M. Psoriasis as a model for T-cell-mediated disease: immunobiologic and clinical effects of treatment with multiple doses of efalizumab, an anti-CD11a antibody. Arch Dermatol 2002, 138, 591-600. doi: 10.1001/archderm.138.5.591.
43. Papp, K.; Bissonnette, R.; Krueger, J. G.; Carey, W.; Gratton, D.; Gulliver, W. P.; Lui, H.; Lynde, C. W.; Magee, A.; Minier, D.; Ouellet, J. P.; Patel, P.; Shapiro, J.; Shear, N. H.; Kramer, S.; Walicke, P.; Bauer, R.; Dedrick, R. L.; Kim, S. S.; White, M.; Garovoy, M. R. The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody. J Am Acad Dermatol 2001, 45, 665-74. doi: 10.1067/mjd.2001.117850.
44. Schulze-Koops, H.; Lipsky, P. E.; Kavanaugh, A. F.; Davis, L. S. Elevated Th1- or Th0-like cytokine mRNA in peripheral circulation of patients with rheumatoid arthritis. Modulation by treatment with anti-ICAM-1 correlates with clinical benefit. J Immunol 1995, 155, 5029-37.
45. Kavanaugh, A. F.; Davis, L. S.; Jain, R. I.; Nichols, L. A.; Norris, S. H.; Lipsky, P. E. A phase I/II open label study of the safety and efficacy of an anti-ICAM-1 (intercellular adhesion molecule-1; CD54) monoclonal antibody in early rheumatoid arthritis. J Rheumatol 1996, 23, (8), 1338-44.
46. Isobe, M.; Yagita, H.; Okumura, K.; Ihara, A. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Science 1992, 255, 1125-7. doi: 10.1126/science.1347662.
47. Takazawa, K.; Hosoda, Y.; Bashuda, H.; Seino, K.; Yagita, H.; Tamatani, T.; Miyasaka, M.; Okumura, K. Synergistic effects of mycophenolate mofetil (MMF, RS-61443) and anti-LFA-1/ICAM-1 monoclonal antibodies on the prolongation of heart allograft survival in rats. Transplant Proc 1996, 28, 1980-1.
48. Gordon, K. B.; Papp, K. A.; Hamilton, T. K.; Walicke, P. A.; Dummer, W.; Li, N.; Bresnahan, B. W.; Menter, A.; Efalizumab Study, G. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA 2003, 290, 3073-80. doi: 10.1001/jama.290.23.3073.
49. Dubertret, L.; Sterry, W.; Bos, J. D.; Chimenti, S.; Shumack, S.; Larsen, C. G.; Shear, N. H.; Papp, K. A.; Group, C. M. S. CLinical experience acquired with the efalizumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque psoriasis: results from a phase III international randomized, placebo-controlled trial. Br J Dermatol 2006, 155, 170-81. doi: 10.1111/j.1365-2133.2006.07344.x.
50. Li, S.; Wang, H.; Peng, B.; Zhang, M.; Zhang, D.; Hou, S.; Guo, Y.; Ding, J. Efalizumab binding to the LFA-1 alphaL I domain blocks ICAM-1 binding via steric hindrance. Proc Natl Acad Sci U S A 2009, 106, 4349-54. PMC: PMC2657446. doi: 10.1073/pnas.0810844106.
51. Major, E. O. Progressive multifocal leukoencephalopathy in patients on immunomodulatory therapies. Annu Rev Med 2010, 61, 35-47. doi: 10.1146/annurev.med.080708.082655.
52. Berger, J. R.; Houff, S. A.; Major, E. O. Monoclonal antibodies and progressive multifocal leukoencephalopathy. MAbs 2009, 1, 583-9. PMC: PMC2791316. doi: 10.4161/mabs.1.6.9884.
53. Miller, D. H.; Khan, O. A.; Sheremata, W. A.; Blumhardt, L. D.; Rice, G. P.; Libonati, M. A.; Willmer-Hulme, A. J.; Dalton, C. M.; Miszkiel, K. A.; O'Connor, P. W.; International Natalizumab Multiple Sclerosis Trial, G. A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2003, 348, 15-23. doi: 10.1056/NEJMoa020696.
54. Ghosh, S.; Goldin, E.; Gordon, F. H.; Malchow, H. A.; Rask-Madsen, J.; Rutgeerts, P.; Vyhnalek, P.; Zadorova, Z.; Palmer, T.; Donoghue, S.; Natalizumab Pan-European Study, G. Natalizumab for active Crohn's disease. N Engl J Med 2003, 348, 24-32. doi: 10.1056/NEJMoa020732.
55. Kuchroo, V. K.; Das, M. P.; Brown, J. A.; Ranger, A. M.; Zamvil, S. S.; Sobel, R. A.; Weiner, H. L.; Nabavi, N.; Glimcher, L. H. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995, 80, 707-18. doi: 10.1016/0092-8674(95)90349-6.
56. Miller, S. D.; Vanderlugt, C. L.; Lenschow, D. J.; Pope, J. G.; Karandikar, N. J.; Dal Canto, M. C.; Bluestone, J. A. Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity 1995, 3, 739-45. doi: 10.1016/1074-7613(95)90063-2.
57. Lenschow, D. J.; Ho, S. C.; Sattar, H.; Rhee, L.; Gray, G.; Nabavi, N.; Herold, K. C.; Bluestone, J. A. Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J Exp Med 1995, 181, 1145-55. PMC: PMC2191918. doi: 10.1084/jem.181.3.1145.
58. Liu, J. Q.; Bai, X. F.; Shi, F. D.; Xiao, B. G.; Li, H. L.; Levi, M.; Mustafa, M.; Wahren, B.; Link, H. Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99. Int Immunol 1998, 10, 1139-48. doi: 10.1093/intimm/10.8.1139.
59. Karin, N.; Mitchell, D. J.; Brocke, S.; Ling, N.; Steinman, L. Reversal of experimental autoimmune encephalomyelitis by a soluble peptide variant of a myelin basic protein epitope: T cell receptor antagonism and reduction of interferon gamma and tumor necrosis factor alpha production. J Exp Med 1994, 180, 2227-37. PMC: PMC2191798. doi: 10.1084/jem.180.6.2227.
60. Larche, M.; Wraith, D. C. Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat Med 2005, 11, S69-76. doi: 10.1038/nm1226.
61. Chao, C. C.; Sytwu, H. K.; Chen, E. L.; Toma, J.; McDevitt, H. O. The role of MHC class II molecules in susceptibility to type I diabetes: identification of peptide epitopes and characterization of the T cell repertoire. Proc Natl Acad Sci U S A 1999, 96, 9299-304. PMC: PMC17775. doi: 10.1073/pnas.96.16.9299.
62. Liu, J.; Purdy, L. E.; Rabinovitch, S.; Jevnikar, A. M.; Elliott, J. F. Major DQ8-restricted T-cell epitopes for human GAD65 mapped using human CD4, DQA1*0301, DQB1*0302 transgenic IA(null) NOD mice. Diabetes 1999, 48, 469-77. doi: 10.2337/diabetes.48.3.469.
63. Wraith, D. C. How to Design Immunotherapeutic Peptides. . Innovations in Pharmaceutical Technology 2006, 44-48.
64. Viner, N. J.; Nelson, C. A.; Deck, B.; Unanue, E. R. Complexes generated by the binding of free peptides to class II MHC molecules are antigenically diverse compared with those generated by intracellular processing. J Immunol 1996, 156, 2365-8.
65. Badawi, A. H.; Siahaan, T. J. Suppression of MOG- and PLP-induced experimental autoimmune encephalomyelitis using a novel multivalent bifunctional peptide inhibitor. J Neuroimmunol 2013, 263, 20-7. PMC: PMC4139121. doi: 10.1016/j.jneuroim.2013.07.009.
66. Anderton, S. M.; Wraith, D. C. Hierarchy in the ability of T cell epitopes to induce peripheral tolerance to antigens from myelin. Eur J Immunol 1998, 28, 1251-61. doi: 10.1002/(SICI)1521-4141(199804)28:04<1251::AID-IMMU1251>3.0.CO;2-O.
67. Yu, P.; Gregg, R. K.; Bell, J. J.; Ellis, J. S.; Divekar, R.; Lee, H. H.; Jain, R.; Waldner, H.; Hardaway, J. C.; Collins, M.; Kuchroo, V. K.; Zaghouani, H. Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen. J Immunol 2005, 174, 6772-80. doi: 10.4049/jimmunol.174.11.6772.
68. Hedegaard, C. J.; Krakauer, M.; Bendtzen, K.; Lund, H.; Sellebjerg, F.; Nielsen, C. H. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 2008, 125, 161-9. PMC: PMC2561132. doi: 10.1111/j.1365-2567.2008.02837.x.
69. Wildbaum, G.; Netzer, N.; Karin, N. Tr1 cell-dependent active tolerance blunts the pathogenic effects of determinant spreading. J Clin Invest 2002, 110, 701-10. PMC: PMC151104. doi: 10.1172/JCI15176.
70. Tuohy, V. K.; Lu, Z.; Sobel, R. A.; Laursen, R. A.; Lees, M. B. Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice. J Immunol 1989, 142, 1523-7.
71. Streeter, H.; Pillai, S.; Scolding, N.; Wraith, D., ATX-MS1467, a therapeutic peptide vaccine for treatment of multiple sclerosis. In World Congress on Treatment and Research in MS, 2008.
72. Chataway, J.; Martin, K.; Barrell, K.; Sharrack, B.; Stolt, P.; Wraith, D. C.; Group, A.-M. S. Effects of ATX-MS-1467 immunotherapy over 16 weeks in relapsing multiple sclerosis. Neurology 2018, 90, e955-e962. doi: 10.1212/WNL.0000000000005118.
73. Corthay, A.; Backlund, J.; Holmdahl, R. Role of glycopeptide-specific T cells in collagen-induced arthritis: an example how post-translational modification of proteins may be involved in autoimmune disease. Ann Med 2001, 33, 456-65. doi: 10.3109/07853890109002094.
74. Dzhambazov, B.; Nandakumar, K. S.; Kihlberg, J.; Fugger, L.; Holmdahl, R.; Vestberg, M. Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules. J Immunol 2006, 176, 1525-33. doi: 10.4049/jimmunol.176.3.1525.
75. Myers, L. K.; Sakurai, Y.; Tang, B.; He, X.; Rosloniec, E. F.; Stuart, J. M.; Kang, A. H. Peptide-induced suppression of collagen-induced arthritis in HLA-DR1 transgenic mice. Arthritis Rheum 2002, 46, 3369-77. doi: 10.1002/art.10687.
76. Bayrak, S.; Mitchison, N. A. Bystander suppression of murine collagen-induced arthritis by long-term nasal administration of a self type II collagen peptide. Clin Exp Immunol 1998, 113, 92-5. PMC: PMC1905015. doi: 10.1046/j.1365-2249.1998.00638.x.
77. Bayrak, S.; Holmdahl, R.; Travers, P.; Lauster, R.; Hesse, M.; Dolling, R.; Mitchison, N. A. T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes. Int Immunol 1997, 9, 1687-99. doi: 10.1093/intimm/9.11.1687.
78. Hammer, J.; Gallazzi, F.; Bono, E.; Karr, R. W.; Guenot, J.; Valsasnini, P.; Nagy, Z. A.; Sinigaglia, F. Peptide binding specificity of HLA-DR4 molecules: correlation with rheumatoid arthritis association. J Exp Med 1995, 181, 1847-55. PMC: PMC2191993. doi: 10.1084/jem.181.5.1847.
79. Lubberts, E. IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 2008, 41, 84-91. doi: 10.1016/j.cyto.2007.09.014.
80. Lubberts, E.; van den Bersselaar, L.; Oppers-Walgreen, B.; Schwarzenberger, P.; Coenen-de Roo, C. J.; Kolls, J. K.; Joosten, L. A.; van den Berg, W. B. IL-17 promotes bone erosion in murine collagen-induced arthritis through loss of the receptor activator of NF-kappa B ligand/osteoprotegerin balance. J Immunol 2003, 170, 2655-62. doi: 10.4049/jimmunol.170.5.2655.
81. Kuchroo, V. K.; Greer, J. M.; Kaul, D.; Ishioka, G.; Franco, A.; Sette, A.; Sobel, R. A.; Lees, M. B. A single TCR antagonist peptide inhibits experimental allergic encephalomyelitis mediated by a diverse T cell repertoire. J Immunol 1994, 153, 3326-36.
82. Nicholson, L. B.; Murtaza, A.; Hafler, B. P.; Sette, A.; Kuchroo, V. K. A T cell receptor antagonist peptide induces T cells that mediate bystander suppression and prevent autoimmune encephalomyelitis induced with multiple myelin antigens. Proc Natl Acad Sci U S A 1997, 94, 9279-84. PMC: PMC23155. doi: 10.1073/pnas.94.17.9279.
83. Duda, P. W.; Schmied, M. C.; Cook, S. L.; Krieger, J. I.; Hafler, D. A. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest 2000, 105, 967-76. PMC: PMC377485. doi: 10.1172/JCI8970.
84. Stern, J. N.; Keskin, D. B.; Zhang, H.; Lv, H.; Kato, Z.; Strominger, J. L. Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci U S A 2008, 105, 5172-6. PMC: PMC2278190. doi: 10.1073/pnas.0712131105.
85. Musio, S.; Pedotti, P.; Mantegazza, R.; Ohtsu, H.; Boon, L.; Steinman, L.; Galli, S. J.; Pedotti, R. Anaphylaxis to a self-peptide in the absence of mast cells or histamine. Lab Invest 2009, 89, 398-405. doi: 10.1038/labinvest.2009.4.
86. Candia, M.; Kratzer, B.; Pickl, W. F. On Peptides and Altered Peptide Ligands: From Origin, Mode of Action and Design to Clinical Application (Immunotherapy). Int Arch Allergy Immunol 2016, 170, 211-233. PMC: PMC7058415. doi: 10.1159/000448756.
87. Hill, J. A.; Southwood, S.; Sette, A.; Jevnikar, A. M.; Bell, D. A.; Cairns, E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol 2003, 171, 538-41. doi: 10.4049/jimmunol.171.2.538.
88. Mamula, M. J.; Gee, R. J.; Elliott, J. I.; Sette, A.; Southwood, S.; Jones, P. J.; Blier, P. R. Isoaspartyl post-translational modification triggers autoimmune responses to self-proteins. J Biol Chem 1999, 274, 22321-7. doi: 10.1074/jbc.274.32.22321.
89. McAdam, S. N.; Fleckenstein, B.; Rasmussen, I. B.; Schmid, D. G.; Sandlie, I.; Bogen, B.; Viner, N. J.; Sollid, L. M. T cell recognition of the dominant I-A(k)-restricted hen egg lysozyme epitope: critical role for asparagine deamidation. J Exp Med 2001, 193, 1239-46. PMC: PMC2193382. doi: 10.1084/jem.193.11.1239.
90. Nakashima, K.; Hagiwara, T.; Ishigami, A.; Nagata, S.; Asaga, H.; Kuramoto, M.; Senshu, T.; Yamada, M. Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1alpha,25-dihydroxyvitamin D(3). J Biol Chem 1999, 274, 27786-92. doi: 10.1074/jbc.274.39.27786.
91. Kim, J. K.; Mastronardi, F. G.; Wood, D. D.; Lubman, D. M.; Zand, R.; Moscarello, M. A. Multiple sclerosis: an important role for post-translational modifications of myelin basic protein in pathogenesis. Mol Cell Proteomics 2003, 2, 453-62. doi: 10.1074/mcp.M200050-MCP200.
92. Makrygiannakis, D.; af Klint, E.; Lundberg, I. E.; Lofberg, R.; Ulfgren, A. K.; Klareskog, L.; Catrina, A. I. Citrullination is an inflammation-dependent process. Ann Rheum Dis 2006, 65, 1219-22. PMC: PMC1798285. doi: 10.1136/ard.2005.049403.
93. W Dieterich, T. E., M Bauer, P Donner, U Volta, E O Riecken, D Schuppan. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Medicine 1997, 3, 797-801. doi: 10.1038/nm0797-797.
94. Elli, L.; Bergamini, C. M.; Bardella, M. T.; Schuppan, D. Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver. Dig Liver Dis 2009, 41, 541-50. doi: 10.1016/j.dld.2008.12.095.
95. C S Greenberg, P. J. B., R H Rice. Transglutaminases: multifunctional cross-linking enzymes that stabilize tissues FASEB journal 1991, 5, 3071-3077. doi: 10.1096/fasebj.5.15.1683845.
96. Jiang Xia, M. S., Elin Bergseng, Ludvig M Sollid, Chaitan Khosla. Inhibition of HLA-DQ2-Mediated Antigen Presentation by Analogues of a High Affinity 33-Residue Peptide from r2-Gliadin. Journal of the American Chemical Society 2006, 128, 1859-1867. doi: 10.1021/ja056423o.
97. Janeway, C. A. Immunotherapy by peptides? Nature 1989, 341, 541-544.
98. Acha-Orbea, H.; Mitchell, D. J.; Timmermann, L.; Wraith, D. C.; Tausch, G. S.; Waldor, M. K.; Zamvil, S. S.; McDevitt, H. O.; Steinman, L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 1988, 54, 263-73. doi: 10.1016/0092-8674(88)90558-2.
99. F R Burns, X. B. L., N Shen, H Offner, Y K Chou, A A Vandenbark, E Heber-Katz. Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar V alpha and V beta chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. Journal of Experimental Medicine 1989, 169, 27-39. doi: 10.1084/jem.169.1.27.
100. Urban, J. L.; Kumar, V.; Kono, D. H.; Gomez, C.; Horvath, S. J.; Clayton, J.; Ando, D. G.; Sercarz, E. E.; Hood, L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 1988, 54, 577-92. doi: 10.1016/0092-8674(88)90079-7.
101. Laura Santambrogio, M. B. L., Raymond A. Sobel. Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS. Journal of Neuroimmunology 1997, 81, 1-13. doi: 10.1016/s0165-5728(97)00138-0.
102. Santambrogio, L.; Lees, M. B.; Sobel, R. A. Altered peptide ligand modulation of experimental allergic encephalomyelitis: immune responses within the CNS. J Neuroimmunol 1998, 81, 1-13. doi: 10.1016/s0165-5728(97)00138-0.
103. Kobayashi, N.; Kobayashi, H.; Gu, L.; Malefyt, T.; Siahaan, T. J. Antigen-specific suppression of experimental autoimmune encephalomyelitis by a novel bifunctional peptide inhibitor. J Pharmacol Exp Ther 2007, 322, 879-86. doi: 10.1124/jpet.107.123257.
104. Raffaele De Palma, S. W., Federica Sallusto, Gabriella Di Felice, Paola Martucci, Domenico Geraci, Paolo Colombo, Costantino Troise, Guido Sacerdoti, Arcangelo Nocera, Jack Gorski. Use of Antagonist Peptides to Inhibit In Vitro T Cell Responses to Par j1, the Major Allergen of Parietaria judaica Pollen. Journal of Immunology 1999, 162,1982-1987.
105. Sloan-Lancaster, J.; Evavold, B. D.; Allen, P. M. Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature 1993, 363, 156-9. doi: 10.1038/363156a0.
106. Chen, Z.; Andreev, D.; Oeser, K.; Krljanac, B.; Hueber, A.; Kleyer, A.; Voehringer, D.; Schett, G.; Bozec, A. Th2 and eosinophil responses suppress inflammatory arthritis. Nat Commun 2016, 7, 11596. PMC: PMC4899615. doi: 10.1038/ncomms11596.
107. Stefanova, I.; Hemmer, B.; Vergelli, M.; Martin, R.; Biddison, W. E.; Germain, R. N. TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol 2003, 4, 248-54. doi: 10.1038/ni895.
108. Dennis C. Wylie, J. D., Arup K. Chakraborty. Sensitivity of T cells to antigen and antagonism emerges from differential regulation of the same molecular signaling module. PNAS 2007, 104, 223-240. doi: 10.1007/978-3-030-57204-4.
109. Bauer, L.; Bohle, B.; Jahn-Schmid, B.; Wiedermann, U.; Daser, A.; Renz, H.; Kraft, D.; Ebner, C. Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1. Clin Exp Immunol 1997, 107, 536-41. PMC: PMC1904612. doi: 10.1046/j.1365-2249.1997.d01-953.x.
110. Vieira, P. L.; Christensen, J. R.; Minaee, S.; O'Neill, E. J.; Barrat, F. J.; Boonstra, A.; Barthlott, T.; Stockinger, B.; Wraith, D. C.; O'Garra, A. IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 2004, 172, 5986-93. doi: 10.4049/jimmunol.172.10.5986.
111. L Kappos, G. C., H Panitch, J Oger, J Antel, P Conlon, L Steinman. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nature Medicine 2000, 6, 1176-1182. doi: 10.1038/80525.
112. Kim, H. J.; Antel, J. P.; Duquette, P.; Alleva, D. G.; Conlon, P. J.; Bar-Or, A. Persistence of immune responses to altered and native myelin antigens in patients with multiple sclerosis treated with altered peptide ligand. Clin Immunol 2002, 104, 105-14. doi: 10.1006/clim.2002.5258.
113. Norman, P. S.; Ohman, J. L., Jr.; Long, A. A.; Creticos, P. S.; Gefter, M. A.; Shaked, Z.; Wood, R. A.; Eggleston, P. A.; Hafner, K. B.; Rao, P.; Lichtenstein, L. M.; Jones, N. H.; Nicodemus, C. F. Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med 1996, 154, 1623-8. doi: 10.1164/ajrccm.154.6.8970345.
114. Pfeiffer, C.; Murray, J.; Madri, J.; Bottomly, K. Selective activation of Th1- and Th2-like cells in vivo--response to human collagen IV. Immunol Rev 1991, 123, 65-84. doi: 10.1111/j.1600-065x.1991.tb00606.x.
115. Paul R. Rogers, G. H. a. S. L. S. High Antigen Density and IL-2 Are Required for Generation of CD4 Effectors Secreting Th1 Rather Than Th0 Cytokines. Journal of Immunology 1998, 161, 3844-3852.
116. Saraiva, M.; Christensen, J. R.; Veldhoen, M.; Murphy, T. L.; Murphy, K. M.; O'Garra, A. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 2009, 31, 209-19. PMC: PMC2791889. doi: 10.1016/j.immuni.2009.05.012.
117. X Tao, C. G., S Constant and K Bottomly. Induction of IL-4-producing CD4+ T cells by antigenic peptides altered for TCR binding. Journal of Immunology 1997, 158, 4237-4244.
118. Katsara, M.; Yuriev, E.; Ramsland, P. A.; Tselios, T.; Deraos, G.; Lourbopoulos, A.; Grigoriadis, N.; Matsoukas, J.; Apostolopoulos, V. Altered peptide ligands of myelin basic protein ( MBP87-99 ) conjugated to reduced mannan modulate immune responses in mice. Immunology 2009, 128, 521-33. PMC: PMC2792136. doi: 10.1111/j.1365-2567.2009.03137.x.
119. Tian, D. H.; Perera, C. J.; Apostolopoulos, V.; Moalem-Taylor, G. Effects of vaccination with altered Peptide ligand on chronic pain in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Front Neurol 2013, 4, 168. PMC: PMC3810649. doi: 10.3389/fneur.2013.00168.
120. J Sloan-Lancaster, P. M. A. Significance of T-cell stimulation by altered peptide ligands in T cell biology. Current Opinion in Immunologu 1995, 7, 103-109. Pdoi: 10.1016/0952-7915(95)80035-2.
121. Sloan-Lancaster, J.; Shaw, A. S.; Rothbard, J. B.; Allen, P. M. Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell 1994, 79, 913-22. doi: 10.1016/0092-8674(94)90080-9.
122. J van Bergen, F. K. Altered peptide ligands and wild-type peptide induce indistinguishable responses of a human Th0 clone. Eurpoean Journal of Immunology 1998, 28, 2801-2808. doi: 10.1002/(SICI)1521-4141(199809)28:09<2801::AID-IMMU2801>3.0.CO;2-N.
123. D A Peterson, R. J. D., O Kanagawa, E R Unanue. Quantitative Analysis of the T Cell Repertoire that Escapes Negative Selection. Immunity 1999, 11, 453-462. doi: 10.1016/s1074-7613(00)80120-x.
124. Falk, K.; Lau, J. M.; Santambrogio, L.; Esteban, V. M.; Puentes, F.; Rotzschke, O.; Strominger, J. L. Ligand exchange of major histocompatibility complex class II proteins is triggered by H-bond donor groups of small molecules. J Biol Chem 2002, 277, 2709-15. doi: 10.1074/jbc.M109098200.
125. Yusuf-Makagiansar, H.; Anderson, M. E.; Yakovleva, T. V.; Murray, J. S.; Siahaan, T. J. Inhibition of LFA-1/ICAM-1 and VLA-4/VCAM-1 as a therapeutic approach to inflammation and autoimmune diseases. Med Res Rev 2002, 22, 146-67. doi: 10.1002/med.10001.
126. Shimaoka, M.; Springer, T. A. Therapeutic antagonists and the conformational regulation of the beta2 integrins. Curr Top Med Chem 2004, 4, 1485-95. doi: 10.2174/1568026043387575.
127. Kallen, J.; Welzenbach, K.; Ramage, P.; Geyl, D.; Kriwacki, R.; Legge, G.; Cottens, S.; Weitz-Schmidt, G.; Hommel, U. Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol 1999, 292, 1-9. doi: 10.1006/jmbi.1999.3047.
128. Shannon, J. P.; Silva, M. V.; Brown, D. C.; Larson, R. S. Novel cyclic peptide inhibits intercellular adhesion molecule-1-mediated cell aggregation. J Pept Res 2001, 58, 140-50. doi: 10.1034/j.1399-3011.2001.00899.x.
129. Gadek, T. R.; Burdick, D. J.; McDowell, R. S.; Stanley, M. S.; Marsters, J. C., Jr.; Paris, K. J.; Oare, D. A.; Reynolds, M. E.; Ladner, C.; Zioncheck, K. A.; Lee, W. P.; Gribling, P.; Dennis, M. S.; Skelton, N. J.; Tumas, D. B.; Clark, K. R.; Keating, S. M.; Beresini, M. H.; Tilley, J. W.; Presta, L. G.; Bodary, S. C. Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule. Science 2002, 295, 1086-9. doi: 10.1126/science.295.5557.1086.
130. Anderson, M. E.; Siahaan, T. J. Targeting ICAM-1/LFA-1 interaction for controlling autoimmune diseases: designing peptide and small molecule inhibitors. Peptides 2003, 24, (3), 487-501. doi: 10.1016/s0196-9781(03)00083-4.
131. Anderson, M. E.; Siahaan, T. J. Mechanism of binding and internalization of ICAM-1-derived cyclic peptides by LFA-1 on the surface of T cells: a potential method for targeted drug delivery. Pharm Res 2003, 20, 1523-32. doi: 10.1023/a:1026188212126.
132. Anderson, M. E.; Tejo, B. A.; Yakovleva, T.; Siahaan, T. J. Characterization of binding properties of ICAM-1 peptides to LFA-1: inhibitors of T-cell adhesion. Chem Biol Drug Des 2006, 68, 20-8. doi: 10.1111/j.1747-0285.2006.00407.x.
133. Anderson, M. E.; Yakovleva, T.; Hu, Y.; Siahaan, T. J. Inhibition of ICAM-1/LFA-1-mediated heterotypic T-cell adhesion to epithelial cells: design of ICAM-1 cyclic peptides. Bioorg Med Chem Lett 2004, 14, 1399-402. doi: 10.1016/j.bmcl.2003.09.100.
134. Yusuf-Makagiansar, H.; Makagiansar, I. T.; Hu, Y.; Siahaan, T. J. Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction. Peptides 2001, 22, 1955-62. doi: 10.1016/s0196-9781(01)00546-0.
135. Yusuf-Makagiansar, H.; Makagiansar, I. T.; Siahaan, T. J. Inhibition of the adherence of T-lymphocytes to epithelial cells by a cyclic peptide derived from inserted domain of lymphocyte function-associated antigen-1. Inflammation 2001, 25, 203-14. doi: 10.1023/a:1011044616170.
136. Yusuf-Makagiansar, H.; Siahaan, T. J. Binding and internalization of an LFA-1-derived cyclic peptide by ICAM receptors on activated lymphocyte: a potential ligand for drug targeting to ICAM-1-expressing cells. Pharm Res 2001, 18, 329-35. doi: 10.1023/a:1011007014510.
137. Makagiansar, I. T.; Yusuf-Makagiansar, H.; Ikesue, A.; Calcagno, A. M.; Murray, J. S.; Siahaan, T. J. N-cadherin involvement in the heterotypic adherence of malignant T-cells to epithelia. Mol Cell Biochem 2002, 233, 1-8. doi: 10.1023/a:1015556625038.
138. Xu, C. R.; Yusuf-Makagiansar, H.; Hu, Y.; Jois, S. D.; Siahaan, T. J. Structural and ICAM-1-docking properties of a cyclic peptide from the I-domain of LFA-1: an inhibitor of ICAM-1/LFA- 1-mediated T-cell adhesion. J Biomol Struct Dyn 2002, 19, 789-99. doi: 10.1080/07391102.2002.10506785.
139. Yusuf-Makagiansar, H.; Yakovleva, T. V.; Tejo, B. A.; Jones, K.; Hu, Y.; Verkhivker, G. M.; Audus, K. L.; Siahaan, T. J. Sequence recognition of alpha-LFA-1-derived peptides by ICAM-1 cell receptors: inhibitors of T-cell adhesion. Chem Biol Drug Des 2007, 70, 237-46. doi: 10.1111/j.1747-0285.2007.00549.x.
140. Murray, J. S.; Oney, S.; Page, J. E.; Kratochvil-Stava, A.; Hu, Y.; Makagiansar, I. T.; Brown, J. C.; Kobayashi, N.; Siahaan, T. J. Suppression of type 1 diabetes in NOD mice by bifunctional peptide inhibitor: modulation of the immunological synapse formation. Chem Biol Drug Des 2007, 70, 227-36. doi: 10.1111/j.1747-0285.2007.00552.x.
141. Kobayashi, N.; Kiptoo, P.; Kobayashi, H.; Ridwan, R.; Brocke, S.; Siahaan, T. J. Prophylactic and therapeutic suppression of experimental autoimmune encephalomyelitis by a novel bifunctional peptide inhibitor. Clin Immunol 2008, 129, 69-79. PMC: PMC2597351. doi: 10.1016/j.clim.2008.06.002.
142. Zhao, H.; Kiptoo, P.; Williams, T. D.; Siahaan, T. J.; Topp, E. M. Immune response to controlled release of immunomodulating peptides in a murine experimental autoimmune encephalomyelitis (EAE) model. J Control Release 2010, 141, 145-52. PMC: PMC3903655. doi: 10.1016/j.jconrel.2009.09.002.
143. Buyuktimkin, B.; Wang, Q.; Kiptoo, P.; Stewart, J. M.; Berkland, C.; Siahaan, T. J. Vaccine-like controlled-release delivery of an immunomodulating peptide to treat experimental autoimmune encephalomyelitis. Mol Pharm 2012, 9, 979-85. PMC: PMC3357633. doi: 10.1021/mp200614q.
144. Floris, S.; Blezer, E. L.; Schreibelt, G.; Dopp, E.; van der Pol, S. M.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain 2004, 127, 616-27. doi: 10.1093/brain/awh068.
145. Badawi, A. H.; Kiptoo, P.; Wang, W. T.; Choi, I. Y.; Lee, P.; Vines, C. M.; Siahaan, T. J. Suppression of EAE and prevention of blood-brain barrier breakdown after vaccination with novel bifunctional peptide inhibitor. Neuropharmacology 2012, 62, 1874-81. PMC: PMC3269550. doi: 10.1016/j.neuropharm.2011.12.013.
146. Lock, C.; Hermans, G.; Pedotti, R.; Brendolan, A.; Schadt, E.; Garren, H.; Langer-Gould, A.; Strober, S.; Cannella, B.; Allard, J.; Klonowski, P.; Austin, A.; Lad, N.; Kaminski, N.; Galli, S. J.; Oksenberg, J. R.; Raine, C. S.; Heller, R.; Steinman, L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 2002, 8, 500-8. doi: 10.1038/nm0502-500.
147. Manikwar, P.; Buyuktimkin, B.; Kiptoo, P.; Badawi, A. H.; Galeva, N. A.; Williams, T. D.; Siahaan, T. J. I-domain-antigen conjugate (IDAC) for delivering antigenic peptides to APC: synthesis, characterization, and in vivo EAE suppression. Bioconjug Chem 2012, 23, 509-17. PMC: PMC3311109. doi: 10.1021/bc200580j.
148. Manikwar, P.; Tejo, B. A.; Shinogle, H.; Moore, D. S.; Zimmerman, T.; Blanco, F.; Siahaan, T. J. Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics 2011, 1, 277-89. PMC: PMC3100608. doi: 10.7150/thno/v01p0277.
149. Buyuktimkin, B.; Manikwar, P.; Kiptoo, P. K.; Badawi, A. H.; Stewart, J. M., Jr.; Siahaan, T. J. Vaccinelike and prophylactic treatments of EAE with novel I-domain antigen conjugates (IDAC): targeting multiple antigenic peptides to APC. Mol Pharm 2013, 10, 297-306. PMC: PMC3540176. doi: 10.1021/mp300440x.
150. Moral, M. E. G.; Siahaan, T. J. Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against Cancer and Autoimmune Diseases. Curr Top Med Chem 2017, 17, (32), 3425-3443. PMC: PMC5835217. doi: 10.2174/1568026618666180118154514.
151. Masteller, E. L.; Warner, M. R.; Tang, Q.; Tarbell, K. V.; McDevitt, H.; Bluestone, J. A. Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J Immunol 2005, 175, 3053-9. doi: 10.4049/jimmunol.175.5.3053.
152. Bour-Jordan, H.; Esensten, J. H.; Martinez-Llordella, M.; Penaranda, C.; Stumpf, M.; Bluestone, J. A. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family. Immunol Rev 2011, 241, 180-205. PMC: PMC3077803. doi: 10.1111/j.1600-065X.2011.01011.x.
153. Chittasupho, C.; Sestak, J.; Shannon, L.; Siahaan, T. J.; Vines, C. M.; Berkland, C. Hyaluronic acid graft polymers displaying peptide antigen modulate dendritic cell response in vitro. Mol Pharm 2014, 11, 367-73. PMC: PMC3927369. doi: 10.1021/mp4003909.
154. Kuehl, C.; Thati, S.; Sullivan, B.; Sestak, J.; Thompson, M.; Siahaan, T.; Berkland, C. Pulmonary Administration of Soluble Antigen Arrays Is Superior to Antigen in Treatment of Experimental Autoimmune Encephalomyelitis. J Pharm Sci 2017, 106, 3293-3302. PMC: PMC5643236. doi: 10.1016/j.xphs.2017.06.008.
155. Sestak, J.; Mullins, M.; Northrup, L.; Thati, S.; Forrest, M. L.; Siahaan, T. J.; Berkland, C. Single-step grafting of aminooxy-peptides to hyaluronan: a simple approach to multifunctional therapeutics for experimental autoimmune encephalomyelitis. J Control Release 2013, 168, 334-40. PMC: PMC3672265. doi: 10.1016/j.jconrel.2013.03.015.
156. Sestak, J. O.; Fakhari, A.; Badawi, A. H.; Siahaan, T. J.; Berkland, C. Structure, size, and solubility of antigen arrays determines efficacy in experimental autoimmune encephalomyelitis. AAPS J 2014, 16, 1185-93. PMC: PMC4389745. doi: 10.1208/s12248-014-9654-z.
157. Sestak, J. O.; Sullivan, B. P.; Thati, S.; Northrup, L.; Hartwell, B.; Antunez, L.; Forrest, M. L.; Vines, C. M.; Siahaan, T. J.; Berkland, C. Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis. Mol Ther Methods Clin Dev 2014, 1, 14008. PMC: PMC4420258. doi: 10.1038/mtm.2014.8.
158. Thati, S.; Kuehl, C.; Hartwell, B.; Sestak, J.; Siahaan, T.; Forrest, M. L.; Berkland, C. Routes of administration and dose optimization of soluble antigen arrays in mice with experimental autoimmune encephalomyelitis. J Pharm Sci 2015, 104, 714-21. PMC: PMC4312227. doi: 10.1002/jps.24272.
159. Hunter, Z.; McCarthy, D. P.; Yap, W. T.; Harp, C. T.; Getts, D. R.; Shea, L. D.; Miller, S. D. A biodegradable nanoparticle platform for the induction of antigen-specific immune tolerance for treatment of autoimmune disease. ACS Nano 2014, 8,2148-60. PMC: PMC3990004. doi: 10.1021/nn405033r.
160. Getts, D. R.; Martin, A. J.; McCarthy, D. P.; Terry, R. L.; Hunter, Z. N.; Yap, W. T.; Getts, M. T.; Pleiss, M.; Luo, X.; King, N. J.; Shea, L. D.; Miller, S. D. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nat Biotechnol 2012, 30, 1217-24. PMC: PMC3589822. doi: 10.1038/nbt.2434.
161. Saito, E.; Kuo, R.; Kramer, K. R.; Gohel, N.; Giles, D. A.; Moore, B. B.; Miller, S. D.; Shea, L. D. Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease. Biomaterials 2019, 222, 119432. PMC: PMC6830542. doi: 10.1016/j.biomaterials.2019.119432.
162. Pickens, C. J.; Christopher, M. A.; Leon, M. A.; Pressnall, M. M.; Johnson, S. N.; Thati, S.; Sullivan, B. P.; Berkland, C. Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders. Mol Pharm 2019, 16, (6), 2452-2461. PMC: PMC7590940. doi: 10.1021/acs.molpharmaceut.9b00063.
163. Kim, M. K.; Kim, J. Properties of immature and mature dendritic cells: phenotype, morphology, phagocytosis, and migration. RSC Advances 2019, 9, (20), 11230-11238. doi: 10.1039/c9ra00818g.