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

Hdl Handle:
http://hdl.handle.net/10034/620461
Title:
MHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escape
Authors:
Pymm, Phillip; Illing, 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.
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.
Affiliation:
Monash University; University of Chester; Cardiff University School of Medicine; National Institutes of Health; University of Melbourne;
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.
Publisher:
Macmillan Publishers
Journal:
Nature Structural & Molecular Biology
Publication Date:
20-Feb-2017
URI:
http://hdl.handle.net/10034/620461
DOI:
10.1038/nsmb.3381
Additional Links:
http://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3381.html
Type:
Article
Language:
en
Description:
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:
1545-9993
EISSN:
1545-9985
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorPymm, Phillipen
dc.contributor.authorIlling, Patriciaen
dc.contributor.authorRamarathinam, Srien
dc.contributor.authorO'Connor, Geraldine Men
dc.contributor.authorHughes, Victoria A.en
dc.contributor.authorHitchen, Corinneen
dc.contributor.authorPrice, David A.en
dc.contributor.authorHo, Boscoen
dc.contributor.authorMcVicar, Daniel Wen
dc.contributor.authorBrooks, Andrew G.en
dc.contributor.authorPurcell, Anthony Wen
dc.contributor.authorRossjohn, Jamieen
dc.contributor.authorVivian, Julian P.en
dc.date.accessioned2017-03-31T10:09:01Z-
dc.date.available2017-03-31T10:09:01Z-
dc.date.issued2017-02-20-
dc.identifier.citationPymm, 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.en
dc.identifier.issn1545-9993-
dc.identifier.doi10.1038/nsmb.3381-
dc.identifier.urihttp://hdl.handle.net/10034/620461-
dc.descriptionThis 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.en
dc.description.abstractMajor 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.en
dc.language.isoenen
dc.publisherMacmillan Publishersen
dc.relation.urlhttp://www.nature.com/nsmb/journal/vaop/ncurrent/full/nsmb.3381.htmlen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectImmunologyen
dc.subjectX-ray crystallographyen
dc.subjectHLAen
dc.subjectKIRen
dc.titleMHC-I peptides get out of the groove and enable a novel mechanism of HIV-1 escapeen
dc.typeArticleen
dc.identifier.eissn1545-9985-
dc.contributor.departmentMonash University; University of Chester; Cardiff University School of Medicine; National Institutes of Health; University of Melbourne;en
dc.identifier.journalNature Structural & Molecular Biologyen
dc.date.accepted2017-01-20-
or.grant.openaccessYesen
rioxxterms.funderNational Health and Medical Research Council of Australia; Australian Research Councilen
rioxxterms.identifier.projectExternal fundingen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2017-08-20-
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