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

Argaet, Victor P., Schmidt, Christopher W., Burrows, Scott R., Silins, Sharon L., Kurilla, Mike G., Doolan, Denise L., Suhrbier, Andreas, Moss, Denis J., Kieff, Elliot, Sculley, Tom B., and Misko, Ihor S. (1994) Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus. The Journal of Experimental Medicine, 180 (6). pp. 2335-2340.

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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.

Item ID: 42783
Item Type: Article (Refereed Research - C1)
ISSN: 1540-9538
Funders: National Health and Medical Research Council (NHMRC) Australia, National Institutes of Health (NIH)
Projects and Grants: NHMRC/NIH CA-52250
Date Deposited: 23 Mar 2016 04:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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