The Evolution of the Major Histocompatibility Complex in Birds

The genetic region that scientists today call the major histocompatibility complex (MHC) was discovered in the 1930s by Peter Gorer in his pioneering studies of antigenic responses to transplanted sera by inbred mouse strains (Gorer 1936). The MHC was genetically defined more precisely by George Snell (1948), who first used the term. Contrary to what many believe, the discovery of cellular antigens in chickens (Gallus gallus), which have functions similar to those in mice, occurred before comparable discoveries in humans (Briles and McGibbon 1948). Thus, studies of the MHC in birds have more than a 50-year history. The immunological and molecular biological revolutions of the 1970s and 1980s, culminating most recently in the complete sequencing of (a) the human leukocyte antigen (HLA; Beck et al. 1999) and (b) the B complex in chickens (Kaufman et al. 1999), revealed that the vertebrate MHC is a complex, multigene family comprising loci encoding receptors on the surfaces of a variety of immune and nonimmune cells. These receptors bind amino acid fragments (or peptides) from foreign pathogens, upon which a cascade of immunological events known as the adaptive immune response is initiated (figure 1). The fundamental position of MHC molecules for initiation and maintenance of both the T cell-mediated and humoral (antibody) arms of the adaptive immune responses has led some immunologists to conclude that the MHC is “the center of the immune universe” (Trowsdale 1995).