期刊
IMMUNITY
卷 38, 期 3, 页码 425-436出版社
CELL PRESS
DOI: 10.1016/j.immuni.2012.11.021
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资金
- ANR, Sidaction [ANR-09-JCJC-0114-01]
- French ANRS
- National Institutes of Health via the Intramural Program of the Vaccine Research Center (National Institute of Allergy and Infectious Diseases)
- Australian Research Council (ARC)
- Australian National Health and Medical Research Council (NHMRC)
- UK Biotechnology and Biological Sciences Research Council [BB/H001085/1]
- Japanese Ministry of Health [18390141]
- Global COE program (Global Education and Research Center Aiming at the Control of AIDS'') of the Japanese Ministry of Education, Science, Sports, and Culture
- Sidaction Fellowship
- Agence Nationale de la Recherche (ANR) [ANR-09-JCJC-0114] Funding Source: Agence Nationale de la Recherche (ANR)
- Grants-in-Aid for Scientific Research [18390141] Funding Source: KAKEN
- Biotechnology and Biological Sciences Research Council [BB/H001085/1] Funding Source: researchfish
- Wellcome Trust [100326/Z/12/Z] Funding Source: researchfish
- BBSRC [BB/H001085/1] Funding Source: UKRI
The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear. Here, we investigated protective HIV-1-specific CD8(+) T cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK(263-272)) presented by human leukocyte antigen (HLA)-B*2705. We found that cross-reactive CD8(+) T cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B*2705(+) individuals. A protective CD8(+) T cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.
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