Journal
JOURNAL OF VIROLOGY
Volume 82, Issue 15, Pages 7357-7368Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00607-08
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Funding
- MRC [G0501963] Funding Source: UKRI
- Medical Research Council [G0501963] Funding Source: researchfish
- Intramural NIH HHS Funding Source: Medline
- Medical Research Council [G0501963] Funding Source: Medline
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T-cell receptors (TCRs) govern the specificity, efficacy, and cross-reactivity of CD8 T cells. Here, we studied CD8 T-cell clonotypes from Mane-A*10(+) pigtail macaques responding to the simian immunodeficiency virus (SIV) Gag KP9 epitope in a setting of vaccination and subsequent viral challenge. We observed a diverse TCR repertoire after DNA, recombinant poxvirus, and live attenuated virus vaccination, with none of 59 vaccine-induced KP9-specific TCRs being identical between macaques. The KP9-specific TCR repertoires remained diverse after SIV or simian-human immunodeficiency virus challenge but, remarkably, exhibited substantially different clonotypic compositions compared to the corresponding populations prechallenge. Within serial samples from individual pigtail macaques, only a small subset (33.9%) of TCRs induced by vaccination were maintained or expanded after challenge. Most (66.1%) of the TCRs induced by vaccination were not detectable after challenge. Our results suggest that some CD8 T cells induced by vaccination are more efficient than others at responding to a viral challenge. These findings have implications for future AIDS virus vaccine studies, which should consider the fitness of vaccine-induced T cells in order to generate robust responses in the face of virus exposure.
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