Abstract
How the naive T cell repertoire arises and forms the memory repertoire is still poorly understood. This relationship was analyzed by taking advantage of the focused TCR usage in HLA-A2-restricted CD8 memory T cell responses to influenza M1(58-66). We analyzed rearranged BV19 genes from CD8 single-positive thymocytes, a surrogate for the naive repertoire, from 10 HLA-A2 individuals. CDR3 amino acid sequences associated with response to influenza were observed at higher frequencies than expected by chance, an indicator of preselection. We propose that a rearrangement mechanism involving long P-nucleotide addition from the J2.7 region explains part of this increase. Special rearrangement mechanisms can result in identical T cells in different individuals, referred to as public responses. Indeed, the rearrangements utilizing long P nucleotide additions were commonly observed in the response to the M1(58-66) epitope in 30 HLA-A2 middle-aged adults. Thus, in addition to negative and positive selection, special rearrangement mechanisms may influence the composition of the naive repertoire, resulting in more robust responses to a pathogen in some individuals.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adult
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CD8 Antigens / biosynthesis
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CD8 Antigens / genetics
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / virology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Clone Cells
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Complementarity Determining Regions / genetics
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism
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Gene Rearrangement, T-Lymphocyte / immunology*
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HLA-A2 Antigen / genetics
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HLA-A2 Antigen / immunology*
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Humans
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Immunoglobulin Joining Region / genetics
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Immunoglobulin Variable Region / genetics
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Immunologic Memory / genetics*
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Middle Aged
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Resting Phase, Cell Cycle / genetics
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Resting Phase, Cell Cycle / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / virology
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Viral Matrix Proteins / chemistry
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / metabolism
Substances
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CD8 Antigens
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Complementarity Determining Regions
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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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Immunoglobulin Joining Region
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Immunoglobulin Variable Region
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M1 protein, Influenza A virus
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Viral Matrix Proteins