Abstract
To understand how thymic selection gives rise to T cells that are capable of major histocompatibility complex (MHC)-restricted recognition of antigen but are tolerant of self, we directly examined how peptide/MHC ligands expressed on thymic epithelial cells trigger the positive selection of immature thymocytes. We demonstrate that abundant self-peptides, purified from the H-2D(b) molecules of thymic epithelial cells, are specifically recognized during the positive selection of CD8+ T cells, implying that positive selection generates a repertoire of T cells that is weakly self-reactive. We also found that this recognition is somewhat cross-reactive, thereby providing an explanation for how the specific recognition of a limited repertoire of thymic self-peptides can select a diverse repertoire of T cells.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Autoantigens / immunology*
-
Autoantigens / isolation & purification
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation / immunology
-
Cell Line
-
Cytotoxicity, Immunologic
-
Epithelium / immunology
-
Female
-
Fetus
-
Lymphocyte Activation*
-
Lymphocytic choriomeningitis virus / immunology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Organ Culture Techniques
-
Peptide Fragments / immunology*
-
Peptide Fragments / isolation & purification
-
Receptors, Antigen, T-Cell, alpha-beta / genetics
-
Receptors, Antigen, T-Cell, alpha-beta / immunology
-
T-Lymphocytes, Cytotoxic / immunology*
-
T-Lymphocytes, Cytotoxic / metabolism
-
T-Lymphocytes, Cytotoxic / virology
-
Thymus Gland / cytology
-
Thymus Gland / immunology*
Substances
-
Autoantigens
-
Peptide Fragments
-
Receptors, Antigen, T-Cell, alpha-beta