A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition
Author
Macdonald, WA; Purcell, AW; Misfud, NA; Ely, LK; Williams, DS; Chang, LN; Gorman, J; Clements, CS; Kjer-Nielsen, L; Koelle, DM; ...Date
2003-09-01Source Title
JOURNAL OF EXPERIMENTAL MEDICINEPublisher
ROCKEFELLER UNIV PRESSUniversity of Melbourne Author/s
PURCELL, ANTHONY; WILLIAMS, DAVID; Kjer-Nielsen, Lars; Tait, Brian; Brooks, Andrew; McCluskey, James; CHANG, LINUS; MACDONALD, WHITNEY ALISON; MIFSUD, NICOLE ANDREAAffiliation
Microbiology And ImmunologyMetadata
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Journal ArticleCitations
Macdonald, 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. https://doi.org/10.1084/jem.20030066.Access Status
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194191Description
C1 - Journal Articles Refereed
Abstract
HLA-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.
Keywords
Cellular Immunology; Immune System and AllergyExport Reference in RIS Format
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