Show simple item record

dc.contributor.authorZernich, D
dc.contributor.authorPurcell, AW
dc.contributor.authorMacdonald, WA
dc.contributor.authorKjer-Nielsen, L
dc.contributor.authorEly, LK
dc.contributor.authorLaham, N
dc.contributor.authorCrockford, T
dc.contributor.authorMifsud, NA
dc.contributor.authorBharadwaj, M
dc.contributor.authorChang, L
dc.contributor.authorTait, BD
dc.contributor.authorHoldsworth, R
dc.contributor.authorBrooks, AG
dc.contributor.authorBottomley, SP
dc.contributor.authorBeddoe, T
dc.contributor.authorPeh, CA
dc.contributor.authorRossjohn, J
dc.contributor.authorMcCluskey, J
dc.date.available2014-05-21T19:21:14Z
dc.date.issued2004-07-05
dc.identifierpii: jem.20031680
dc.identifier.citationZernich, D., Purcell, A. W., Macdonald, W. A., Kjer-Nielsen, L., Ely, L. K., Laham, N., Crockford, T., Mifsud, N. A., Bharadwaj, M., Chang, L., Tait, B. D., Holdsworth, R., Brooks, A. G., Bottomley, S. P., Beddoe, T., Peh, C. A., Rossjohn, J. & McCluskey, J. (2004). Natural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. JOURNAL OF EXPERIMENTAL MEDICINE, 200 (1), pp.13-24. https://doi.org/10.1084/jem.20031680.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/26153
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractHLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.subjectImmunogenetics ; Infectious Diseases; Immune System and Allergy
dc.titleNatural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20031680
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMicrobiology And Immunology
melbourne.source.titleJOURNAL OF EXPERIMENTAL MEDICINE
melbourne.source.volume200
melbourne.source.issue1
melbourne.source.pages13-24
dc.research.coderfcd320204
dc.research.codeseo1998730101
dc.research.codeseo1998730102
dc.rights.licenseCC BY-NC-SA
melbourne.publicationid28344
melbourne.elementsid263171
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213310
melbourne.contributor.authorPURCELL, ANTHONY
melbourne.contributor.authorKjer-Nielsen, Lars
melbourne.contributor.authorBharadwaj, Mandvi
melbourne.contributor.authorTait, Brian
melbourne.contributor.authorBrooks, Andrew
melbourne.contributor.authorMcCluskey, James
melbourne.contributor.authorCHANG, LINUS
melbourne.contributor.authorMIFSUD, NICOLE
melbourne.contributor.authorBURNS, DANIELLE
melbourne.contributor.authorMACDONALD, WHITNEY ALISON
melbourne.contributor.authorLAHAM, NIHAY
melbourne.contributor.authorCROCKFORD, TANYA LEE
dc.identifier.eissn1540-9538
melbourne.accessrightsAccess this item via the Open Access location


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record