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The Journal of Immunology
Article . 2011 . Peer-reviewed
License: OUP Standard Publication Reuse
Data sources: Crossref
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Naive T Cell Repertoire Skewing in HLA-A2 Individuals by a Specialized Rearrangement Mechanism Results in Public Memory Clonotypes

Authors: Maryam, Yassai; Dmitry, Bosenko; Melissa, Unruh; Gregory, Zacharias; Erica, Reed; Wendy, Demos; Andrea, Ferrante; +1 Authors

Naive T Cell Repertoire Skewing in HLA-A2 Individuals by a Specialized Rearrangement Mechanism Results in Public Memory Clonotypes

Abstract

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.

Keywords

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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    16
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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
16
Average
Average
Top 10%
bronze