Evidence against a dimeric structure for membrane-bound HLA antigens

Abstract

HUMAN histocompatibility (HLA) antigens are expressed on the surfaces of almost all cell types and according to various criteria are integral membrane glycoproteins¹. They are composed of equimolar amounts of two dissimilar polypeptide chains which are non-covalently linked and which have molecular weights of about 43,000 and 12,000 as judged by polyacrylamide gel electrophoresis in sodium dodecyl sulphate (SDS)^2–4. The larger chain carries the polymorphic allogeneic specificities and all of the carbohydrate². The smaller chain represents β₂-microglobulin, whose amino acid sequence shows marked homology to the C_H3-domain of the γ-1 chain of immunoglobulin G (ref. 5). This homology and other arguments have led to the proposals that HLA antigens and immunoglobulins have a common evolutionary origin^6,7, and that HLA antigens have an immunoglobulin-like structure in which two basic units of one each of the larger and smaller polypeptide chains are linked either non-covalently⁸ or by a disulphide bridge^9,10 to give a 4-chain dimer of molecular weight 110,000. In contrast to the latter proposal, some results presented here suggest that HLA antigens do not have a dimeric structure.