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 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.
Argaet
V P
VP
Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
Schmidt
C W
CW
Burrows
S R
SR
Silins
S L
SL
Kurilla
M G
MG
Doolan
D L
DL
Suhrbier
A
A
Moss
D J
DJ
Kieff
E
E
Sculley
T B
TB
Misko
I S
IS
D000595:Amino Acid Sequence; D001483:Base Sequence; D002353:Carrier State / Q000276:immunology*; D002999:Clone Cells; D017124:Conserved Sequence; D017931:DNA Primers; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006566:Herpesviridae Infections / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D013601:T-Lymphocytes / Q000382:microbiology* / Q000821:virology; D014412:Tumor Virus Infections / Q000276:immunology*
D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta