Pymm, Phillip, Illing, Patricia T., Ramarathinam, Sri H., O'Connor, Geraldine M., Hughes, Victoria A., Hitchen, Corinne, Price, David A.  ORCID: https://orcid.org/0000-0001-9416-2737, Ho, Bosco K., McVicar, Daniel W., Brooks, Andrew G., Purcell, Anthony W., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Vivian, Julian P.
2017.
MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape.
Nature Structural and Molecular Biology
24
, pp. 387-394.
10.1038/nsmb.3381
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Abstract
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*57:01-TW10 epitope is governed by a ‘molecular tension’ between the adaptive and innate immune systems.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | Nature Publishing Group |
| ISSN: | 1545-9993 |
| Date of First Compliant Deposit: | 2 June 2017 |
| Date of Acceptance: | 20 January 2017 |
| Last Modified: | 20 Nov 2024 01:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/101075 |
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