Among candidate genes, the MHC class II molecule is the most comprehensively studied. MHC polymorphisms are associated with development of RA, SLE, MS, TID, and other autoimmune diseases. RA is a striking example. A shared epitope, consisting of a 5-aminoacid sequence notif in the third allelic hypervariable region of the HLA-DRβ1 chain (QKRAA in the *0401 allele, QRRAA in the *0404 and *0101 alleles), is carried by 90% of patients with RA and is associated with disease severity. In addition to MHC-linked genes, mutations or genetic polymorphisms involving non MHC genes also are strong candidates for autoimmune disease susceptibility genes. These include genetic polymorphisms or deficiency of molecules involved in the response to or clearance of immune complexes, which are associated with SLE, as well as genes influencing T cell activation, cytokine responses, or programmed cell death.