Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus

doi:10.1084/jem.180.6.2335

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Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus

VP Argaet, CW Schmidt, SR Burrows, SL Silins, MG Kurilla, DL Doolan, A Suhrbier, DJ Moss, E Kieff and TB Suclley
Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.

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.
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