MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape
Authors
Pymm, PhillipIlling, Patricia
Ramarathinam, Sri
O'Connor, Geraldine M.
Hughes, Victoria A.
Hitchen, Corinne
Price, David A.
Ho, Bosco
McVicar, Daniel W.
Brooks, Andrew G.
Purcell, Anthony W.
Rossjohn, Jamie
Vivian, Julian P.
Affiliation
Monash University; University of Chester; Cardiff University School of Medicine; National Institutes of Health; University of Melbourne;Publication Date
2017-02-20
Metadata
Show full item recordAbstract
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.Citation
Pymm, P., Illing, P. T., Ramarathinam, S. H., O'Connor, G. M., Hughes, V. A., Hitchen, C.,... Vivian, J. P. (2017). MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape. Nature Structural & Molecular Biology, 24, 387-394.Publisher
Nature ResearchAdditional Links
http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3381.htmlType
ArticleLanguage
enDescription
This document is the Accepted Manuscript version of a published work that appeared in final form in Nature Structural & Molecular Biology. To access the final edited and published work see http://dx.doi.org/10.1038/nsmb.3381.ISSN
1545-9993EISSN
1545-9985ae974a485f413a2113503eed53cd6c53
10.1038/nsmb.3381
Scopus Count
Collections
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/