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Naive T cell repertoire skewing in HLA-A2 individuals by a specialized rearrangement mechanism results in public memory clonotypes.

TitleNaive T cell repertoire skewing in HLA-A2 individuals by a specialized rearrangement mechanism results in public memory clonotypes.
Publication TypeJournal Article
Year of Publication2011
AuthorsYassai, M, Bosenko, D, Unruh, M, Zacharias, G, Reed, E, Demos, W, Ferrante, A, Gorski, J
JournalJ Immunol
Volume186
Issue5
Pagination2970-7
Date Published2011 Mar 1
ISSN1550-6606
KeywordsAdult, Antigens, CD8, CD8-Positive T-Lymphocytes, Cell Differentiation, Clone Cells, Complementarity Determining Regions, Epitopes, T-Lymphocyte, G0 Phase, Gene Rearrangement, T-Lymphocyte, HLA-A2 Antigen, Humans, Immunoglobulin Joining Region, Immunoglobulin Variable Region, Immunologic Memory, Middle Aged, T-Lymphocyte Subsets, Viral Matrix Proteins
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.

DOI10.4049/jimmunol.1002764
Alternate JournalJ. Immunol.
PubMed ID21282510
Grant ListU19 AI062627 / AI / NIAID NIH HHS / United States
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