The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles.
Class II major histocompatibility complex (MHCII) molecules present antigens to CD4(+) 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.
Dai
Shaodong
S
Integrated Department of Immunology, Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Crawford
Frances
F
Marrack
Philippa
P
Kappler
John W
JW
D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D006684:HLA-DR Antigens; D010455:Peptides