Coevolution of HLA-B and PERB11.1 (MICA): Significance of independent triplet expansion within the transmembrane region of PERB11.1 (MICA)

Several highly polymorphic sequences are present in the beta block of the M HC, especially HLA-B, HLA-C, PERB11.1 (MICA), and PERB11.2 (MICB). It is no w apparent that the polymorphism of PERB11.1 is of the same order as that o f HLA-A, -B, and -C and it has been suggested that PERB11 could explain som e of the disease associations previously attributed to HLA-B. Phylogenetic analysis of PERB11 alpha-domain sequences demonstrates relationships with H LA-B cross-reactive serogroups. In contrast, the transmembrane polymorphism s do not appear to be associated with either PERB11 or HLA-B. These data in dicate that PERB11 and HLA-B have evolved in concert from their common ance stors and that the transmembrane polymorphisms have arisen independently an d more recently. MHC disease associations will need to be reviewed in the l ight of mechanisms such as receptor binding and signaling.