Reproducible selection of high avidity CD8~+ T-cell clones following secondary acute virus infection

Tania Cukalac; Jesseka Chadderton; Andreas HandelPeter C. DohertyStephen J. TurnerPaul G. ThomasNicole L. La Gruta

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Reproducible selection of high avidity CD8~+ T-cell clones following secondary acute virus infection

机译：Reproducible selection of high avidity CD8~+ T-cell clones following secondary acute virus infection

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The recall of memory CD8~+ cytotoxic T lymphocytes (CTLs), elicited by prior virus infection or vaccination, is critical for immune protection. The extent to which this arises as a consequence of stochastic clonal expansion vs. active selection of particular clones remains unclear. Using a parallel adoptive transfer protocol in combination with single cell analysis to define the complementarity determining region (CDR) 3α and CDR3β regions of individual Tcell receptor (TCR) heterodimers, we characterized the antigendriven recall of the same memory CTL population in three individual recipients. This high-resolution analysis showed reproducible enrichment (or diminution) of particular TCR clonotypes across all challenged animals. These changes in clonal composition were TCRα- and β chain-dependent and were directly related to the avidity of the TCR for the virus-derived peptide (p) + major histocompatibility complex class I molecule. Despite this shift in clonotype representation indicative of differential selection, there was no evidence of overall repertoire narrowing, suggesting a strategy to optimize CTL responses while safeguarding TCR diversity.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第4期|1485-1490|共6页
作者
Tania Cukalac; Jesseka Chadderton; Andreas HandelPeter C. DohertyStephen J. TurnerPaul G. ThomasNicole L. La Gruta;
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作者单位

Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia;

Department of Epidemiology and Biostatistics, College of Public Health, University of Georgia, Athens, GA 30602;

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
recall CD8~+ T-cell response; clonal selection; antiviral immunity; memory CD8~+ T cells; influenza virus;

Reproducible selection of high avidity CD8~+ T-cell clones following secondary acute virus infection

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