Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape

Pymm, Phillip, Illing, Patricia T., Ramarathinam, Sri H., O'Connor, Geraldine M., Hughes, Victoria A., Hitchen, Corinne, Price, David A. ORCID:, Ho, Bosco K., McVicar, Daniel W., Brooks, Andrew G., Purcell, Anthony W., Rossjohn, Jamie ORCID: 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

[thumbnail of 101075   MHCI peptides  Rossjohn-Pymm  FIGS.pdf]
PDF - Accepted Post-Print Version
Download (15MB) | Preview


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: 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: 09 Nov 2023 22:27

Citation Data

Cited 23 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item


Downloads per month over past year

View more statistics