| Literature DB >> 7964506 |
V P Argaet1, C W Schmidt, S R Burrows, S L Silins, M G Kurilla, D L Doolan, A Suhrbier, D J Moss, E Kieff, T B Sculley, I S Misko.
Abstract
To examine T cell receptor (TCR) diversity involved in the memory response to a persistent human pathogen, we determined nucleotide sequences encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8+ cytotoxic T cell clones specific for an immunodominant epitope (FLRGRAYGL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show that identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conservatively at only two residues. This dominant selection of alpha and beta chain rearrangements suggest that a persistent viral infection can select for a highly focused memory response and indicates a strong bias in gene segment usage and recombination. A novel double-step semiquantitative polymerase chain reaction (PCR) procedure and direct sequencing of amplified TCR cDNA from fresh lymphocytes derived from three HLA-B8 individuals detected transcripts specific for the conserved beta chain in an EBV-seropositive donor but not in two seronegative donors. This report describes an unprecedented degree of conservation in TCR selected in response to a natural persistent infection.Entities:
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Year: 1994 PMID: 7964506 PMCID: PMC2191762 DOI: 10.1084/jem.180.6.2335
Source DB: PubMed Journal: J Exp Med ISSN: 0022-1007 Impact factor: 14.307