Abstract
In the thymus, immature T cells are positively and negatively selected by multiple interactions between their Ag receptors (TCRs) and self MHC/peptide complexes expressed on thymic stromal cells. Here we show that in the milieu of negative selection on physiological self class II MHC/peptide complexes (Abwt), a single class II/peptide complex AbEp52-68 positively selects a number of TCRs with various Ag specificities. This TCR repertoire is semidiverse and not biased toward Ep-like Ags. Our finding implies that the degeneracy of positive selection for peptide ligands exceeds peptide-specific negative selection and is essential to increase the efficiency and diversity of the repertoire so that T cells with the same Ag specificity can be selected by different self MHC/ peptide complexes.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Autoantigens / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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Epitopes, T-Lymphocyte / analysis*
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Histocompatibility Antigens Class II / metabolism*
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Immune Tolerance
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Immunophenotyping
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Mice, Transgenic
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Molecular Sequence Data
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Peptides / immunology*
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Peptides / metabolism
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Radiation Chimera
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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 / isolation & purification
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Receptors, Antigen, T-Cell, alpha-beta / analysis
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Sequence Homology, Amino Acid
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class II
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Peptides
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta