Evolutionary relationship between immunoglobulins and transplantation antigens.
The major human and murine histocompatibility antigens are tetrameric molecules with an apparent molecular weight of about 130,000. They are composed of two types of polypeptide chains. The two light chains, previously identified as beta2-microglobulins, are bound to the two heavy, alloantigenic HL-A or H-2 polypeptide chains by noncovalent interactions only. The heavy chains are held together by disulfide bridge(s) located in the part of the molecule that is attached to the cell membrane. By limited proteolysis of the histocompatibility antigens evidence was obtained suggesting that the heavy chain may consist of three compact domains connected by more extended stretches of polypeptide chain. Each domain appeared to contain a single disulfide bride encompassing about 60 to 70 amino-acid residues. Staphylococcus aureus protein A is known to bind exclusively to the Fe region of immunoglobulin G. It was, however, observed that protein  A interacts in a similar way with the H-2 antigen heavy chain. This observation, together  withthe homology of the primary structure of beta2-microglobulin to immunoglobulin G, the tetrameric structure of the alloantigens, the ogranizations of the heavy polypeptide chain into compact domains, and the presence of a single, immunoglobulin-like disulfide loop in each domain, establishes a close similarity in structure between histocompatibility antigens and immunoglobulins. The similarity in structural features suggests a  common evolutionary origin of the two types of molecules.
D000818:Animals; D001665:Binding Sites; D005075:Biological Evolution; D002462:Cell Membrane / Q000276:immunology; D004220:Disulfides; D006680:HLA Antigens; D006649:Histocompatibility Antigens; D006801:Humans; D007136:Immunoglobulins; D046911:Macromolecular Substances; D051379:Mice; D008970:Molecular Weight; D010206:Papain; D011485:Protein Binding; D011487:Protein Conformation; D012995:Solubility; D013154:Spleen / Q000276:immunology
D004220:Disulfides; D006680:HLA Antigens; D006649:Histocompatibility Antigens; D007136:Immunoglobulins; D046911:Macromolecular Substances; D010206:Papain