Abstract
The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC molecules. This reactivity is the basis of specific immune response to the foreign Ag. How such specificities are generated in the thymus is still being debated. Signals generated through TCR upon interaction with self MHC-peptide complexes are critical for maturation of the CD4+ helper and CD8+ cytotoxic subsets. We have observed maturation of CD4+ but not CD8+ T cells in Ly-6A.2 transgenic MHC null mice. Since there can be no interactions with MHC molecules in these mice, these CD4+ cells must express the T cell repertoire that exists before positive and negative selection. Interestingly, despite an absence of selection by MHC molecules, the CD4+ cells that mature recognize MHC molecules at a frequency as high as in CD4+ cells in normal mice. These results demonstrate that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC molecules; and 2) CD4+ cells as opposed to CD8+ cells have distinct lineage commitment signals. These results also suggest that signals originating from Ly-6 can promote or substitute for signals generated from TCR that are required for positive selection. Moreover, this animal model offers a system to study T cell development in the thymus that can provide insights into mechanisms of lineage commitment in developing T cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD*
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Antigens, Differentiation / metabolism
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Antigens, Ly / genetics*
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CD24 Antigen
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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CD40 Antigens / metabolism
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CD40 Ligand
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / immunology
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Cell Movement / immunology
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Down-Regulation / immunology
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Histocompatibility Antigens Class I / biosynthesis*
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Histocompatibility Antigens Class I / genetics*
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class II / biosynthesis*
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Histocompatibility Antigens Class II / genetics*
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Histocompatibility Antigens Class II / immunology
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Hot Temperature
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Hyaluronan Receptors / biosynthesis
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Immunophenotyping
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Ligands
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Lymphocyte Activation
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Lymphoid Tissue / cytology
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Lymphoid Tissue / metabolism
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Transgenic
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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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 / immunology
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Up-Regulation / immunology
Substances
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Antigens, CD
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Antigens, Differentiation
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Antigens, Ly
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CD24 Antigen
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CD40 Antigens
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Cd24a protein, mouse
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Hyaluronan Receptors
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Ligands
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell, alpha-beta
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CD40 Ligand