Naive T cell repertoire skewing in HLA-A2 individuals by a specialized rearrangement mechanism results in public memory clonotypes. J Immunol 2011 Mar 01;186(5):2970-7
Date
02/02/2011Pubmed ID
21282510DOI
10.4049/jimmunol.1002764Scopus ID
2-s2.0-79952744302 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
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.
Author List
Yassai M, Bosenko D, Unruh M, Zacharias G, Reed E, Demos W, Ferrante A, Gorski JMESH terms used to index this publication - Major topics in bold
AdultCD8 Antigens
CD8-Positive T-Lymphocytes
Cell Differentiation
Clone Cells
Complementarity Determining Regions
Epitopes, T-Lymphocyte
Gene Rearrangement, T-Lymphocyte
HLA-A2 Antigen
Humans
Immunoglobulin Joining Region
Immunoglobulin Variable Region
Immunologic Memory
Middle Aged
Resting Phase, Cell Cycle
T-Lymphocyte Subsets
Viral Matrix Proteins