This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1m6o
From Proteopedia
| Line 4: | Line 4: | ||
==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== | ||
| Line 16: | Line 16: | ||
[[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]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:02 2008'' |
Revision as of 11:52, 21 February 2008
|
Crystal Structure of HLA B*4402 in complex with HLA DPA*0201 peptide
Contents |
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
Page seeded by OCA on Thu Feb 21 13:52:02 2008
