1m6o: Difference between revisions
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==Overview== | ==Overview== | ||
HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are | 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== | ==Disease== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Brooks, A | [[Category: Brooks, A G.]] | ||
[[Category: Clements, C | [[Category: Clements, C S.]] | ||
[[Category: Ely, L | [[Category: Ely, L K.]] | ||
[[Category: Gorman, J | [[Category: Gorman, J J.]] | ||
[[Category: Kjer-Nielsen, L.]] | [[Category: Kjer-Nielsen, L.]] | ||
[[Category: Koelle, D | [[Category: Koelle, D M.]] | ||
[[Category: Lovrecz, G | [[Category: Lovrecz, G O.]] | ||
[[Category: Lu, L.]] | [[Category: Lu, L.]] | ||
[[Category: Macdonald, W | [[Category: Macdonald, W A.]] | ||
[[Category: McCluskey, J.]] | [[Category: McCluskey, J.]] | ||
[[Category: Mifsud, N | [[Category: Mifsud, N A.]] | ||
[[Category: Purcell, A | [[Category: Purcell, A W.]] | ||
[[Category: Rossjohn, J.]] | [[Category: Rossjohn, J.]] | ||
[[Category: Williams, D | [[Category: Williams, D S.]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
[[Category: mhc i]] | [[Category: mhc i]] | ||
[[Category: signal]] | [[Category: signal]] | ||
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Revision as of 11:52, 21 February 2008
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Crystal Structure of HLA B*4402 in complex with HLA DPA*0201 peptide
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
1M6O is a Protein complex structure of sequences from Homo sapiens. 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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