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Class II antigens of the major histocompatibility complex (MHC) consist of two glycosylated, membrane-integrated polypeptide chains. These cell surface-expressed molecules are involved in several immunobiological events involving cell-cell interactions, most of which seem to require that genetically identical class II antigens, or other molecules controlled by the same region of the MHC, are expressed on the interacting cells. The extensive genetic polymorphism of the class II antigens has rendered analyses in the human system of the number of non-allelic species of class II antigens difficult, although several laboratories have reported the existence of at least two types of human class II antigens. Here we present the results of experiments using restriction enzyme digestions and separation of DNA from individuals homozygous for the MHC followed by hybridization to human class II antigen alpha- and beta-chain cDNA probes. While the alpha-chain probe gave only a single hybridization band, the various beta-chain probes revealed a more complex pattern that is consistent with the existence of at least three separate beta-chain genes or pseudogenes in the human MHC.

Class II antigens of the major histocompatibility complex (MHC) consist of a family of closely related cell surface-expressed glycoproteins. These antigens, which are genetically polymorphic, control important aspects of the immune response. At least three types of human class II antigens, namely, DR, DC and SB (refs 2-4), have been identified. All class II antigens are heterodimers composed of one alpha- and one beta-chain. The genes for both types of subunits are encompassed within the MHC. The general features of the DC and DR antigens have recently been elucidated. Much less is known, however, about the SB molecules. Here we describe the isolation of a cDNA clone as well as a genomic clone encoding a beta-chain whose amino acid sequence is compatible with the partial amino-terminal sequence of SB beta-chains.

The human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (alpha and beta) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response but several human diseases are also found to be associated with certain HLA-DR antigens. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism associated with the beta-chains which seem, from hybridization studies, to be encoded by several genes. We have therefore used the beta-chain cDNA probe, pDR-beta-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease.