First, certain alleles of MHCII, in particular, HLA-DRB1*04:01, *04:04, *04:05, and *01:01, are strongly associated with RA [1–3], as are genes encoding molecules controlling T cell activation and differentiation (PTPN22, CD28 and CTLA4) [4] [5]. The gene discussed is CD28; the disease is rheumatoid arthritis.