Abstract
The current paradigm of MHC and disease association is efficient binding of autoantigens by disease-associated MHC molecules leading to a T cell-mediated immune response and resultant autoimmune sequelae. Data presented here offer a different model for this association of MHC with autoimmune diabetes. This new explanation suggests that the association of MHC with autoimmunity results from "altered" thymic selection in which high-affinity self-reactive (potentially autoreactive) T cells escape negative selection. This model offers an explanation for the requirement of homozygous MHC class II expression in NOD mice (and in man) in susceptibility to IDDM.
MeSH terms
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Animals
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Antigen Presentation
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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Clonal Deletion
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Diabetes Mellitus / genetics
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Diabetes Mellitus / immunology*
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology
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Disease Susceptibility
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Genes, MHC Class II
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HLA-D Antigens / genetics
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HLA-D Antigens / immunology
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Histocompatibility Antigens Class II / immunology
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Humans
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Major Histocompatibility Complex / genetics
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Major Histocompatibility Complex / immunology*
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Mice
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Mice, Inbred NOD
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Models, Immunological
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Protein Binding
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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T-Lymphocyte Subsets / immunology*
Substances
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HLA-D Antigens
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Histocompatibility Antigens Class II
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Receptors, Antigen, T-Cell, alpha-beta