Presentation of a Self-peptide in Two Distinct Conformations by a Disease-associated HLA-B27 Subtype

The MHC locus on human chromosome 6 harbors the most polymorphic genes in the human genome, and the large number of alleles in human populations has permitted key structural features of MHC class I and class II genes that influence susceptibility to several human autoimmune diseases to be delineated. In this issue, Hülsmeyer et al. adds a new twist to the already rich literature on MHC polymorphisms and human disease (1). The authors determined the crystal structures of two HLA-B27 subtypes (B*2705 and B*2709) with the same self-peptide (pVIPR, derived from vasoactive intestinal peptide type 1 receptor). These two subtypes are remarkable in that they differ only at one heavy chain residue but are differentially associated with susceptibility to ankylosing spondylitis (AS), a chronic inflammatory joint disease. The pVIPR peptide bound in a conventional conformation to both HLA-B27 subtypes but in a second...