Structural and immunological similarities between HLA antigens from three loci.

HLA antigens are coded for by three closely linked loci. The gene products of the first and second locus are known to be very similar in overall structure. Antigens coded for by the third locus were examined with regard to their chemical and immunological relationship to the first and second loci gene products. It is demonstrated that the third locus antigens are composed of two types of polypeptide chains, the smaller of which is identical to beta2-microglobulin. The alloantigenic polypeptide chain has an apparent molecular weight of 48 000 when solubilized by detergen treatment and about 35 000 when released from the cell membrane by proteolysis. These data together with size and shape analyses by gel chromatography and sedimentation velocity determinations show that HLA antigens from the three subloci are indistinguishable with the techniques employed. Suggestive evidence was obtained that the third locus antigens are more sensitive to proteolysis than the first and second locus antigens. The similarity between the three gene products was also evident on cyanogen bromide fragmentation of the polypeptide chains. Furthermore, rabbit antibodies against antigens coded for by the first locus cross-reacted extensively with antigens from the second and third locus. This study therefore lends strong credence to the view that the three HLA antigen subloci have arisen by gene duplications of a common ancestral gene.