HLA associations with rheumatoid arthritis: a piece of the puzzle

HLA molecules play a central role in the immune response by presenting processed antigenic peptides to T cells. In the case of rheumatoid arthritis (RA), a specific sequence present within the peptide binding cleft of HLA class II molecules has been implicated in genetic susceptibility to this disease. Several mechanisms could account for this finding. One possibility, designated determinant selection, rests on the possibility that HLA molecules associated with RA may bind a distinct set of foreign or self antigens that can trigger a T cell response in the joint. Alternatively, HLA molecules may predispose to RA by shaping the T cell repertoire during thymic differentiation in neonatal and early adult life. These 2 mechanisms are not mutually exclusive, and it must be remembered that several other susceptibility genes as well as environmental factors remain to be identified before a comprehensive understanding of RA is achieved.