1n2r

From Proteopedia

Revision as of 14:26, 15 February 2008

A natural selected dimorphism in HLA B*44 alters self, peptide reportoire and T cell recognition.

Overview

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.

Disease

Known diseases associated with this structure: Abacavir hypersensitivity, susceptibility to OMIM:[142830], Hypoproteinemia, hypercatabolic OMIM:[109700], Spondyloarthropathy, susceptibility to, 1 OMIM:[142830], Stevens-Johnson syndrome, carbamazepine-induced, susceptibility to OMIM:[142830]

About this Structure

1N2R is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition., Macdonald WA, Purcell AW, Mifsud NA, Ely LK, Williams DS, Chang L, Gorman JJ, Clements CS, Kjer-Nielsen L, Koelle DM, Burrows SR, Tait BD, Holdsworth R, Brooks AG, Lovrecz GO, Lu L, Rossjohn J, McCluskey J, J Exp Med. 2003 Sep 1;198(5):679-91. Epub 2003 Aug 25. PMID:12939341

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