Selection of a diverse TCR repertoire in response to an Epstein-Barr virus-encoded transactivator protein BZLF1 by CD8+ cytotoxic T lymphocytes during primary and persistent infection

International Immunology
S L SilinsI S Misko

Abstract

We investigated the CD8+ cytotoxic T lymphocyte (CTL) repertoire to an HLA B8-restricted peptide, RAKFKQLLQ, located in the Epstein-Barr virus (EBV) immediate-early protein, BZLF1. Repertoire selection was monitored by determining the TCR beta chain sequences of RAKFKQLLQ-specific CTL established from primary infected and healthy virus carriers. PCR analysis of spontaneous EBV-transformed lymphoblastoid cell lines (LCL) from three individuals with primary infection showed that two were infected with type A and one with type B EBV. Polyclonal and clonal CTL that were generated by stimulating peripheral blood mononuclear cells with an HLA B8+ homozygous LCL lysed T cell blasts pulsed with the peptide, RAKFKQLLQ; lysis of certain HLA B8+ LCL targets was associated with the abundance of BZLF1 transcripts. TCR beta analysis showed that while there was loop length restriction in the putative peptide contact site of all responding beta chains, diverse and unique (non-recurrent) TCR beta clonotypes were selected in individuals during primary infection and continued to emerge after long-term virus exposure. TCR-contact site heterogeneity was excluded as the selective force in diversity generation since the epitope-encoded sequences were...Continue Reading

Citations

Jul 2, 1999·Springer Seminars in Immunopathology·M F Callan, A J McMichael
May 4, 2000·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·A B RickinsonN E Annels
Apr 21, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·D J MossR Khanna
Aug 27, 2010·Science Translational Medicine·Damien PicardPhilippe Musette
Nov 23, 2007·Journal of Virology·Suzanne L ElliottMandvi Bharadwaj
Mar 24, 2007·Annual Review of Immunology·Andrew D HislopAlan B Rickinson
Nov 22, 2000·The Journal of Clinical Investigation·M F CallanA J McMichael
Mar 29, 2014·Clinical and Experimental Immunology·D Cárdenas SierraS M Quijano Gómez
Oct 6, 2000·Annual Review of Microbiology·R Khanna, S R Burrows
Oct 5, 2010·PLoS Pathogens·Martin BergbauerWolfgang Hammerschmidt
Aug 4, 2009·PLoS Pathogens·Yoshitaka SatoTatsuya Tsurumi
Nov 18, 2006·Journal of Leukocyte Biology·Paolo SommaMaria Teresa Fiorillo
Jun 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J A KangB S Kim
Aug 21, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Louise C RowntreeNicole A Mifsud
Oct 25, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·N E AnnelsA B Rickinson
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M K MainiP C Beverley
Jul 10, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc JacobsenStefan H E Kaufmann
Dec 26, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dan KoningDebbie van Baarle

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