New aspects of HLA: perspectives for rheumatoid arthritis

The association of several HLA class II alleles with genetic susceptibility to rheumatoid arthritis (RA) suggests a model in which a three-dimensional conformation of the DR molecule represents the key disease susceptibility element. However, recently found new genes of the HLA-D region may contribute additionally to the susceptibility in particular of genes coding for proteases and transporter channels. Since expression of the class II molecule is a common feature of the autoimmunity process, regulatory polymorphisms of the class II genes may influence the antigen-presenting capacity of the cells. The role of the invariant chain, a 31 kD protein associated with the alpha beta complex, is emphasized in antigen presentation and may provide new insights into the pathogenesis and therapy of autoimmune rheumatoid arthritis.