Effect of a free sulphydryl group on expression of HLA-B27 specificity

Sequence studies indicate that the alpha-1 domain of the HLA-B27 molecule has a characteristic unpaired cysteine residue at position 67, adjacent, because of secondary structure, to a lysine at position 70. Simple chemical considerations predict that this cysteine should have an exceptionally reactive sulphydryl group. We have shown by ELISA and flow cytometry that the binding of some monoclonal antibodies to B27 on lymphoid cell lines can be inhibited by reagents which react with sulphydryl groups. However this inhibition is never complete: the evidence suggests 2 forms of B27 molecule, one of which is already blocked. We propose that some HLA molecules with oxidised sulphydryls are recognised as different from the reduced forms. Whether they are also recognised as foreign will depend on an individual's history of thymic learning. Oxidation to 'foreign' HLA in the adult is likely to predispose to inflammatory reactions.