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Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.
Open accessAbstract
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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Citations
Cited by
HOW TCRS BIND MHCS, PEPTIDES, AND CORECEPTORS
Rudolph, M. G., Stanfield, R. L., & Wilson, I. A. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115658 · Cited by 1,310
Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease
Gate, D., Saligrama, N., Leventhal, O., Yang, A. C., Unger, M. S., Middeldorp, J., Chen, K., Lehallier, B., Channappa, D., De Los Santos, M. B., et al. (2020) · Nature · doi:10.1038/s41586-019-1895-7 · Cited by 992
A Direct Estimate of the Human αβ T Cell Receptor Diversity
Arstila, T. P., Casrouge, A., Baron, V., Even, J., Kanellopoulos, J., & Kourilsky, P. (1999) · Science · doi:10.1126/science.286.5441.958 · Cited by 931
Cellular responses to viral infection in humans: lessons from Epstein–Barr virus
Hislop, A. D., Taylor, G. S., Sauce, D., & Rickinson, A. B. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141553 · Cited by 766
Khan, N., Shariff, N., Cobbold, M., Bruton, R., Ainsworth, J. A., Sinclair, A. J., Nayak, L., & Moss, P. A. H. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.4.1984 · Cited by 754
Metadata
- Authors
- Argaet, V. P., Schmidt, C. W., Burrows, S. R., Silins, S. L., Kurilla, M. G., Doolan, D. L., Suhrbier, A., Moss, D. J., Kieff, E., Sculley, T. B., & Misko, I. S.
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1994-12-01
- Volume
- 180
- Issue
- 6
- Pages
- 2335-2340
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2102571570
- Cited by
- 274
- References
- 0
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Argaet, V. P., Schmidt, C. W., Burrows, S. R., Silins, S. L., Kurilla, M. G., Doolan, D. L., Suhrbier, A., Moss, D. J., Kieff, E., Sculley, T. B., & Misko, I. 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. https://doi.org/10.1084/jem.180.6.2335
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