DOMINANT SELECTION OF AN INVARIANT T-CELL ANTIGEN RECEPTOR IN RESPONSE TO PERSISTENT INFECTION BY EPSTEIN-BARR-VIRUS

To examine T cell receptor (TCR) diversity involved in the memory resp onse to a persistent human pathogen, we determined nucleotide sequence s encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8(+) c ytotoxic T cell clones specific for an immunodominant epitope (FLRGRAY GL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show tha t identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conserv atively at only two residues. This dominant selection of alpha and bet a chain rearrangements suggests that a persistent viral infection can select for a highly focused memory response and indicates a strong bia s in gene segment usage and recombination. A novel double-step semiqua ntitative polymerase chain reaction (PCR) procedure and direct sequenc ing of amplified TCR cDNA from fresh lymphocytes derived from three HL A-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.