Differential oxidation of HLA-B2704 and HLA-B2705 in lymphoblastoid and transfected adherent cells.

MHC class I molecules are predominantly involved in the presentation of antigens from viral proteins to CD8+ T cells of the immune system. However, MHC proteins can also be linked to autoimmune diseases, and the HLA-B27 allele is expressed by 95% of people with the rheumatic condition ankylosing spondylitis (AS). A precise molecular explanation for the association between HLA-B27 and AS is still lacking, although it is known that inappropriately disulfide bonded HLA-B27 heavy chains can be found at both the cell surface and in the endoplasmic reticulum (ER) of HLA-B27 expressing cells. This papers shows that HLA-B27 heavy chain misfolding does not depend on any unpaired cysteine residue per se when HLA-B27 is highly expressed. Also shown is that major differences exist in the disulfide-dependent conformations of two HLA-B27 subtypes, HLA-B2704 and HLA-B2705. The results imply that residues 77, 152, and/or 211 influence the redox potential of the MHC class I heavy chain and suggest that manipulating the redox environment can alter the conformational state of HLA-B27 subtypes.