Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice.
CD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studie...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2011-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00017/full |
| _version_ | 1818249592232214528 |
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| author | Melanie D Leech Antonio eCarrillo-Vico Roland S. Liblau Roland S. Liblau Roland S. Liblau Stephen M Anderton |
| author_facet | Melanie D Leech Antonio eCarrillo-Vico Roland S. Liblau Roland S. Liblau Roland S. Liblau Stephen M Anderton |
| author_sort | Melanie D Leech |
| collection | DOAJ |
| description | CD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type C57BL/6 mice. We show that MOG-/- mice have enhanced sensitivity to immunization with the immunodominant peptide of MOG(35-55), as evidenced by increased expansion of both CD4+ and CD8+ T cell subsets. Most strikingly, CD8+ T cells from MOG-/- mice responded to a novel T cell epitope which binds to MHC class I with high affinity. Despite this, MOG-responsive CD8+ T cells sourced from either wild type or MOG-/- mice failed to initiate CNS inflammation upon transfer to MOG-sufficient mice. In our hands, this capacity was only found in CD4+ T cells. However, MOG-/- CD4+ cells did not show greater pathogenic activity than their wild type counterparts. Our data indicate that, in the presence of endogenous MOG, CD8+ T cells capable of responding to a MHC class I-restricted epitope that can be stably expressed are subject to rigorous control through central and/or peripheral tolerance. |
| first_indexed | 2024-12-12T15:38:56Z |
| format | Article |
| id | doaj.art-784c48f1617b40ceaf5c3f5b871488e5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T15:38:56Z |
| publishDate | 2011-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-784c48f1617b40ceaf5c3f5b871488e52022-12-22T00:19:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242011-05-01210.3389/fimmu.2011.0001710160Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice.Melanie D Leech0Antonio eCarrillo-Vico1Roland S. Liblau2Roland S. Liblau3Roland S. Liblau4Stephen M Anderton5University of EdinburghUniversity of EdinburghUniversité ToulouseInsermCNRSUniversity of EdinburghCD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type C57BL/6 mice. We show that MOG-/- mice have enhanced sensitivity to immunization with the immunodominant peptide of MOG(35-55), as evidenced by increased expansion of both CD4+ and CD8+ T cell subsets. Most strikingly, CD8+ T cells from MOG-/- mice responded to a novel T cell epitope which binds to MHC class I with high affinity. Despite this, MOG-responsive CD8+ T cells sourced from either wild type or MOG-/- mice failed to initiate CNS inflammation upon transfer to MOG-sufficient mice. In our hands, this capacity was only found in CD4+ T cells. However, MOG-/- CD4+ cells did not show greater pathogenic activity than their wild type counterparts. Our data indicate that, in the presence of endogenous MOG, CD8+ T cells capable of responding to a MHC class I-restricted epitope that can be stably expressed are subject to rigorous control through central and/or peripheral tolerance.http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00017/fullMultiple SclerosisT cellstoleranceCD8+ T cellsExperimental autoimmune encephalomyelitismyelin oligodendrocyte glycoprotein |
| spellingShingle | Melanie D Leech Antonio eCarrillo-Vico Roland S. Liblau Roland S. Liblau Roland S. Liblau Stephen M Anderton Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. Frontiers in Immunology Multiple Sclerosis T cells tolerance CD8+ T cells Experimental autoimmune encephalomyelitis myelin oligodendrocyte glycoprotein |
| title | Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. |
| title_full | Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. |
| title_fullStr | Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. |
| title_full_unstemmed | Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. |
| title_short | Recognition of a high affinity MHC class I-restricted epitope of myelin oligodendrocyte glycoprotein by CD8+ T cells derived from autoantigen-deficient mice. |
| title_sort | recognition of a high affinity mhc class i restricted epitope of myelin oligodendrocyte glycoprotein by cd8 t cells derived from autoantigen deficient mice |
| topic | Multiple Sclerosis T cells tolerance CD8+ T cells Experimental autoimmune encephalomyelitis myelin oligodendrocyte glycoprotein |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2011.00017/full |
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