Naive T Cell Repertoire Skewing in HLA-A2 Individuals by a Specialized Rearrangement Mechanism Results in Public Memory Clonotypes
pmid: 21282510
Naive T Cell Repertoire Skewing in HLA-A2 Individuals by a Specialized Rearrangement Mechanism Results in Public Memory Clonotypes
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 M158–66. 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 M158–66 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.
- Bloodcenter of Wisconsin United States
- Gulf Coast Regional Blood Center United States
- Blood Systems Research Institute United States
Adult, CD8 Antigens, Immunoglobulin Variable Region, Epitopes, T-Lymphocyte, Cell Differentiation, CD8-Positive T-Lymphocytes, Middle Aged, Gene Rearrangement, T-Lymphocyte, Complementarity Determining Regions, Resting Phase, Cell Cycle, Clone Cells, Viral Matrix Proteins, T-Lymphocyte Subsets, HLA-A2 Antigen, Humans, Immunoglobulin Joining Region, Immunologic Memory
Adult, CD8 Antigens, Immunoglobulin Variable Region, Epitopes, T-Lymphocyte, Cell Differentiation, CD8-Positive T-Lymphocytes, Middle Aged, Gene Rearrangement, T-Lymphocyte, Complementarity Determining Regions, Resting Phase, Cell Cycle, Clone Cells, Viral Matrix Proteins, T-Lymphocyte Subsets, HLA-A2 Antigen, Humans, Immunoglobulin Joining Region, Immunologic Memory
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