期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 24, 期 4, 页码 387-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb.3381
关键词
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资金
- National Health and Medical Research Council of Australia (NHMRC) [APP1063829, APP1099814]
- Australian Research Council (ARC) [DP150104503]
- Australian Postgraduate Award
- Wellcome Trust
- ARC
- National Institutes of Health, National Cancer Institute
- Wellcome Trust [100326/Z/12/Z] Funding Source: researchfish
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57: 01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove. The common escape mutant TSNLQEQIGW bound HLA-B*57:01 canonically, adopting a dramatically different conformation than the TW10 peptide. This affected recognition by killer cell immunoglobulin-like receptor (KIR) 3DL1 expressed on NK cells. We thus define a previously uncharacterized feature of the human leukocyte antigen class I (HLA-I) immunopeptidome that has implications for viral immune escape. We further suggest that recognition of the HLA-B*57:01TW10 epitope is governed by a `molecular tension' between the adaptive and innate immune systems.
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