Abstract
Thymocytes are positively selected for alphabeta T cell antigen receptors (TCR) that recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. MHC bound peptides participate in positive selection; however, their role has remained controversial. A TCR transgenic mouse was established using a TCR restricted to the MHC class Ib molecule, H2-M3. Having defined H2-M3 as the positively selecting MHC molecule, the severely limited number of H2-M3 binding peptides allowed us to characterize an NADH dehydrogenase subunit 1 (ND1)-derived peptide as the physiological ligand of positive selection. This peptide bears no apparent sequence homology to the cognate peptide, is expressed ubiquitously, and yet does not interfere with peripheral T cells. Our studies also suggest that positive selection becomes promiscuous at high epitope densities.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation / genetics
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Cell Line
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Crosses, Genetic
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Fetus
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H-2 Antigens / genetics*
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H-2 Antigens / metabolism
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Histocompatibility Antigens Class I / genetics*
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Histocompatibility Antigens Class I / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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N-Formylmethionine / immunology
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N-Formylmethionine / metabolism
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NADH Dehydrogenase / immunology
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NADH Dehydrogenase / metabolism
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Oligopeptides / immunology
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Oligopeptides / metabolism
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Organ Culture Techniques
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Receptors, Antigen, T-Cell, alpha-beta / genetics*
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / metabolism
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Tumor Cells, Cultured
Substances
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H-2 Antigens
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H2-M3 antigen
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Histocompatibility Antigens Class I
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Oligopeptides
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Receptors, Antigen, T-Cell, alpha-beta
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N-Formylmethionine
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NADH Dehydrogenase