4d8p

Publication Abstract from PubMed

MHC class II molecules are composed of one alpha-chain and one beta-chain whose membrane distal interface forms the peptide binding groove. Most of the existing knowledge on MHC class II molecules comes from the cis-encoded variants where the alpha- and beta-chain are encoded on the same chromosome. However, trans-encoded class II MHC molecules, where the alpha- and beta-chain are encoded on opposite chromosomes, can also be expressed. We have studied the trans-encoded class II HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention as it may explain the increased risk of certain individuals to type 1 diabetes. We report the X-ray crystal structure of this HLA molecule complexed with a gluten epitope at 3.05 A resolution. The gluten epitope is preferentially recognized in context of the DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease patient. This preferential recognition can be explained by improved HLA binding as the epitope combines the peptide binding motif of DQ2.5 (negative charge at P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any alpha-chain and beta-chain belonging to the same group are expected to form a stable heterodimer.

Structural and functional studies of the trans-encoded HLA-DQ2.3 (DQA1*03:01/DQB1*02:01) molecule.,Tollefsen S, Hotta K, Chen X, Simonsen B, Swaminathan K, Mathews II, Sollid LM, Kim CY J Biol Chem. 2012 Feb 23. PMID:22362761^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.