Abstract
T cell recognition of peptide-MHC is highly specific and is sensitive to very low levels of agonist peptide; however, it is unclear how this effect is achieved or regulated. In this study we show that clustering class I MHC molecules on the cell surface of B lymphoblasts enhances their recognition by mouse and human T cells. We increased clustering of MHC I molecules by two methods, cholesterol depletion and direct cross-linking of a dimerizable MHC construct. Imaging showed that both treatments increased the size and intensity of MHC clusters on the cell surface. Enlarged clusters correlated with enhanced lysis and T cell effector function. Enhancements were peptide-specific and greatest at low concentrations of peptide. Clustering MHC class I enhanced recognition of both strong and weak agonists but not null peptide. Our results indicate that the lateral organization of MHC class I on the cell surface can modulate the sensitivity of T cell recognition of agonist peptide.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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Cell Line, Transformed
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Cell Membrane / genetics
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cholesterol / deficiency
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Cross-Linking Reagents / metabolism
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Cytotoxicity, Immunologic / genetics
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Dimerization
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Dose-Response Relationship, Immunologic
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism*
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Histocompatibility Antigens Class I / physiology
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Humans
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Mice
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Mice, Transgenic
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Peptide Fragments / agonists
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Peptide Fragments / deficiency
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Cross-Linking Reagents
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Cholesterol