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dc.contributor.authorPymm, Phillip*
dc.contributor.authorIlling, Patricia*
dc.contributor.authorRamarathinam, Sri*
dc.contributor.authorO'Connor, Geraldine M.*
dc.contributor.authorHughes, Victoria A.*
dc.contributor.authorHitchen, Corinne*
dc.contributor.authorPrice, David A.*
dc.contributor.authorHo, Bosco*
dc.contributor.authorMcVicar, Daniel W.*
dc.contributor.authorBrooks, Andrew G.*
dc.contributor.authorPurcell, Anthony W.*
dc.contributor.authorRossjohn, Jamie*
dc.contributor.authorVivian, Julian P.*
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, 24, 387-394.
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.
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.
dc.language.isoenen
dc.publisherMacmillan Publishers
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.typeArticle
dc.identifier.eissn1545-9985
dc.contributor.departmentMonash University; University of Chester; Cardiff University School of Medicine; National Institutes of Health; University of Melbourne;
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
html.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.


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