Journal
FRONTIERS IN IMMUNOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2017.01503
Keywords
T-cell; T-cell receptor; HIV; immune escape; MHC
Categories
Funding
- UK Biotechnology and Biological Sciences Research Council [BB/H001085/1]
- Tenovus PhD studentship
- RCUK Fellowship
- National Institute of General Medical Sciences, National Institutes of Health [GM067079]
- NIH [R01 AI096879]
- BBSRC [BB/H001085/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/H001085/1] Funding Source: researchfish
- Tenovus Cancer Care [PhD2009/L20] Funding Source: researchfish
- Wellcome Trust [100327/Z/12/Z] Funding Source: researchfish
Ask authors/readers for more resources
Serial accumulation of mutations to fixation in the SLYNTVATL (SL9) immunodominant, HIV p17 Gag-derived, HLA A2-restricted cytotoxic T lymphocyte epitope produce the SLFNTIAVL triple mutant ultimate escape variant. These mutations in solvent-exposed residues are believed to interfere with TCR recognition, although confirmation has awaited structural verification. Here, we solved a TCR co-complex structure with SL9 and the triple escape mutant to determine the mechanism of immune escape in this eminent system. We show that, in contrast to prevailing hypotheses, the main TCR contact residue is 4N and the dominant mechanism of escape is not via lack of TCR engagement. Instead, mutation of solvent-exposed residues in the peptide destabilise the peptide-HLA and reduce peptide density at the cell surface. These results highlight the extraordinary lengths that HIV employs to evade detection by high-affinity TCRs with a broad peptide-binding footprint and necessitate re-evaluation of this exemplar model of HIV TCR escape.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available