Priming of Autoreactive CD8＋ T Cells Is Inhibited by Immunogenic Peptides Which Are Competitive for Major Histocompatibility Complex Class I Binding
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In the present study, we investigated if priming of autoreactive CD8＋ T cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of Kb-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for Kb binding inhibited IFN-γproduction and proliferation of TRP2-180- specific CD8＋ T cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific CD8＋ T cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive CD8＋ T cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific CD8＋ T cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.
Abstract
In the present study, we investigated if priming of autoreactive CD8＋ T cells would be inhibited by competitive peptides for major histocompatibility complex (MHC) class I binding. We used a mouse model of vitiligo which is induced by immunization of Kb-binding tyrosinase-related protein 2 (TRP2)-180 peptide. Competitive peptides for Kb binding inhibited IFN-γproduction and proliferation of TRP2-180- specific CD8＋ T cells upon ex vivo peptide restimulation, while other MHC class I-binding peptides did not. In mice, the capability of inhibition was influenced by T-cell immunogenicity of the competitive peptides. The competitive peptide with a high T-cell immunogenicity efficiently inhibited priming of TRP2-180-specific CD8＋ T cells in vivo, whereas the competitive peptide with a low T-cell immunogenicity did not. Taken together, the inhibition of priming of autoreactive CD8＋ T cells depends on not only competition of peptides for MHC class I binding but also competitive peptide-specific CD8＋ T cells, suggesting that clonal expansion of autoreactive T cells would be affected by expansion of competitive peptide-specific T cells. This result provides new insights into the development of competitive peptides-based therapy for the treatment of autoimmune diseases.
참고문헌 (19)
- Cooper, G. S., "Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases", J. Autoimmun, 33, pp.197~207 (2009)
- Lee, E., "T cell targeted immunotherapy for autoimmune disease", Autoimmunity, 38, pp.577~596 (2005)
- Bjorkman, P. J., "Structure of the human class I histocompatibility antigen, HLA-A2", Nature, 329, pp.506~512 (1987)
- Bjorkman, P. J., "The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens", Nature, 329, pp.512~518 (1987)
- Babbitt, B. P., "Antigenic competition at the level of peptide-Ia binding", Proc. Natl. Acad. Sci. U. S. A, 83, pp.4509~4513 (1986)
- Adorini, L., "In vivo competition between self peptides and foreign antigens in T-cell activation", Nature, 334, pp.623~625 (1988)
- You, S., "Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo", Clin. Exp. Immunol (2013)
- Porgador, A., "Localization, quantitation, and in situ detection of specific peptide-MHC class I complexes using a monoclonal antibody", Immunity, 6, pp.715~726 (1997)
- Bloom, M. B., "Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma", J. Exp. Med, 185, pp.453~459 (1997)
- Kim, S. K., "Private specificities of CD8 T cell responses control patterns of heterologous immunity", J. Exp. Med, 201, pp.523~533 (2005)
- Karunakaran, K. P., "Immunoproteomic discovery of novel T cell antigens from the obligate intracellular pathogen Chlamydia", J. Immunol, 180, pp.2459~2465 (2008)
- Trobaugh, D. W., "Altered effector functions of virus-specific and virus cross-reactive CD8+ T cells in mice immunized with related flaviviruses", Eur. J. Immunol, 40, pp.1315~1327 (2010)
- Clute, S. C., "Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis", J. Clin. Invest, 115, pp.3602~3612 (2005)
- Yewdell, J. W., "Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses", Annu. Rev. Immunol, 17, pp.51~88 (1999)
- Savir, Y., "Balancing speed and accuracy of polyclonal T cell activation: a role for extracellular feedback", BMC Syst. Biol, 6, pp.111~ (2012)
- Curtsinger, J. M., "CD8+ memory T cells (CD44high, Ly-6C+) are more sensitive than naive cells to (CD44low, Ly-6C-) to TCR", CD8 signaling in response to antigen, 1998, pp.160, 3236~3243
- Veiga-Fernandes, H., "Response of naïve and memory CD8+ T cells to antigen stimulation in vivo", Nat. Immunol, 1, pp.47~53 (2000)
- Reed, C., "Prevalence of seropositivity to pandemic influenza A", H1N1 virus in the United States following the 2009 pandemic, 2012, pp.7, e48187~
- Cannon, M. J., "Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection", Rev. Med. Virol, 20, pp.202~213 (2010)