Abstract
Dysregulation of the T cell-dependent Ab response can lead to numerous immunological disorders, ranging from systemic lupus erythematosus to B cell lymphomas. Cellular processes governed by MHC class II proteins play a major role in this response and its dysregulation. The extent to which processes controlled by the diverse family of MHC class I proteins impact such autoimmune and neoplastic disorders, however, is less clear. In this study, we genetically dissect the contributions of individual MHC class I family members and the pathological processes under their control in the systemic lupus erythematosus-like disease of BXSB.Yaa mice and B cell lymphomagenesis of SJL mice. This study reveals a powerful repressive regulatory axis comprised of MHC class I-dependent CD8(+) T cells and NK cells. These results indicate that the predominant role of the MHC class I protein family in such immunological disorders is to protect from more aggressive diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / pathology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / pathology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / pathology
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H-2 Antigens / genetics
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / physiology*
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Killer Cells, Natural / immunology
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Killer Cells, Natural / pathology
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / mortality
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Lupus Erythematosus, Systemic / prevention & control*
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Lymphoma, B-Cell / immunology*
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Lymphoma, B-Cell / mortality
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Lymphoma, B-Cell / prevention & control*
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Mice
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Mice, Inbred Strains
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Moloney murine leukemia virus / immunology
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beta 2-Microglobulin / deficiency
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beta 2-Microglobulin / genetics
Substances
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H-2 Antigens
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H-2K(K) antigen
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I
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beta 2-Microglobulin