1sys: Difference between revisions
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'''Crystal structure of HLA, B*4403, and peptide EEPTVIKKY''' | '''Crystal structure of HLA, B*4403, and peptide EEPTVIKKY''' | ||
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[[Category: Tait, B D.]] | [[Category: Tait, B D.]] | ||
[[Category: Zernich, D.]] | [[Category: Zernich, D.]] | ||
[[Category: | [[Category: B44]] | ||
[[Category: | [[Category: Class i]] | ||
[[Category: | [[Category: Hla]] | ||
[[Category: | [[Category: Mhc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:17:27 2008'' | |||
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Revision as of 06:17, 3 May 2008
Crystal structure of HLA, B*4403, and peptide EEPTVIKKY
Overview
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
Disease
Known disease associated with this structure: Hypoproteinemia, hypercatabolic OMIM:[109700]
About this Structure
1SYS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion., Zernich D, Purcell AW, Macdonald WA, Kjer-Nielsen L, Ely LK, Laham N, Crockford T, Mifsud NA, Bharadwaj M, Chang L, Tait BD, Holdsworth R, Brooks AG, Bottomley SP, Beddoe T, Peh CA, Rossjohn J, McCluskey J, J Exp Med. 2004 Jul 5;200(1):13-24. Epub 2004 Jun 28. PMID:15226359 Page seeded by OCA on Sat May 3 09:17:27 2008
