The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

Journal Article · Fri Sep 05 04:00:00 EDT 2008 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.0805810105· OSTI ID:1006790

Dai, Shaodong; Crawford, Frances; Marrack, Philippa; Kappler, John W ^[1]

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1. HHMI

Class II major histocompatibility complex (MHCII) molecules present antigens to CD4{sup +} T cells. In addition to the most commonly studied human MHCII isotype, HLA-DR, whose {beta} chain is encoded by the HLA-DRB1 locus, several other isotypes that use the same {alpha} chain but have {beta} chains encoded by other genes. These other DR molecules also are expressed in antigen-presenting cells and are known to participate in peptide presentation to T cells and to be recognized as alloantigens by other T cells. Like some of the HLA-DRB1 alleles, several of these alternate DR molecules have been associated with specific autoimmune diseases and T cell hypersensitivity. Here we present the structure of an HLA-DR molecule (DR52c) containing one of these alternate {beta} chains (HLA-DRB3*0301) bound to a self-peptide derived from the Tu elongation factor. The molecule shares structurally conserved elements with other MHC class II molecules but has some unique features in the peptide-binding groove. Comparison of the three major HLA-DBR3 alleles (DR52a, b, and c) suggests that they were derived from one another by recombination events that scrambled the four major peptide-binding pockets at peptide positions 1, 4, 6, and 9 but left virtually no polymorphisms elsewhere in the molecules.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1006790
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (33) ; 08, 2008 Vol. 105; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ANTIGENS
CHAINS
DISEASES
ELONGATION
GENES
HISTOCOMPATIBILITY COMPLEX
PEPTIDES
RECOMBINATION