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dc.contributor.authorMacdonald, WA
dc.contributor.authorPurcell, AW
dc.contributor.authorMisfud, NA
dc.contributor.authorEly, LK
dc.contributor.authorWilliams, DS
dc.contributor.authorChang, LN
dc.contributor.authorGorman, J
dc.contributor.authorClements, CS
dc.contributor.authorKjer-Nielsen, L
dc.contributor.authorKoelle, DM
dc.contributor.authorBurrows, SR
dc.contributor.authorTait, BD
dc.contributor.authorHoldsworth, R
dc.contributor.authorBrooks, AG
dc.contributor.authorLovrecz, GO
dc.contributor.authorLu, L
dc.contributor.authorRossjohn, J
dc.contributor.authorMcCluskey, J
dc.identifierpii: jem.20030066
dc.identifier.citationMacdonald, W. A., Purcell, A. W., Misfud, N. A., Ely, L. K., Williams, D. S., Chang, L. N., Gorman, J., Clements, C. S., Kjer-Nielsen, L., Koelle, D. M., Burrows, S. R., Tait, B. D., Holdsworth, R., Brooks, A. G., Lovrecz, G. O., Lu, L., Rossjohn, J. & McCluskey, J. (2003). A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition. JOURNAL OF EXPERIMENTAL MEDICINE, 198 (5), pp.679-691.
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractHLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402. Crystal structures of B*4402 and B*4403 show how the polymorphism at position 156 is completely buried and yet alters both the peptide and the heavy chain conformation, relaxing ligand selection by B*4403 compared with B*4402. Thus, the polymorphism between HLA-B*4402 and B*4403 modifies both peptide repertoire and T cell recognition, and is reflected in the paradoxically powerful alloreactivity that occurs across this "minimal" mismatch. The findings suggest that these closely related class I genes are maintained in diverse human populations through their differential impact on the selection of peptide ligands and the T cell repertoire.
dc.subjectCellular Immunology; Immune System and Allergy
dc.titleA naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition
dc.typeJournal Article
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMicrobiology And Immunology
melbourne.source.titleJournal of Experimental Medicine
dc.rights.licenseCC BY-NC-SA
melbourne.contributor.authorPURCELL, ANTHONY
melbourne.contributor.authorWILLIAMS, DAVID
melbourne.contributor.authorKjer-Nielsen, Lars
melbourne.contributor.authorTait, Brian
melbourne.contributor.authorBrooks, Andrew
melbourne.contributor.authorMcCluskey, James
melbourne.contributor.authorCHANG, LINUS
melbourne.contributor.authorMACDONALD, WHITNEY ALISON
melbourne.contributor.authorMIFSUD, NICOLE ANDREA
melbourne.accessrightsAccess this item via the Open Access location

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