BINDING OF GLUTEN-DERIVED PEPTIDES TO THE HLA-DQ2 (ALPHA-1-ASTERISK-0501, BETA-1-ASTERISK-0201) MOLECULE, ASSESSED IN A CELLULAR-ASSAY

The nature of the immunopathogenic relationship underlying the very st rong association of coeliac disease (CD) to the HLA-DQ (A10501, B1*02 01) genotype is not known, but probably relates to binding of gluten-d erived epitopes to the HLA-DQ (alpha 10501, beta 1*0201) heterodimer (DQ2). These epitopes have not yet been defined. In this study we have tested the binding of various gluten-derived peptides to DQ2 in a cel lular assay using Epstein-Barr virus (EBV)-transformed B lymphocytes a nd murine fibroblast transfectants. One of these peptides (peptide A), which has previously been shown to exacerbate the CD lesion iii vitro and in vivo, was found to bind to DQ2, albeit only moderately, lendin g further credence to its possible role in the pathogenesis of CD. The nature of peptide A's binding to DQ2 was explored with truncated and conservative point substituted analogues and compared with the publish ed DQ2 binding motif, the results of which explain the observed level of binding.