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.
Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.
V P Argaet, 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; Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.. J Exp Med 1 December 1994; 180 (6): 2335–2340. doi: https://doi.org/10.1084/jem.180.6.2335
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