Structure of the A2m(1) allotype of human IgA--a recombinant molecule.
The complete amino-acid sequence of the constant (C) region of the alpha2 heavy chain of a human IgA2 protein of the A2m(1) allotype has been determined. Excluding the hinge region and the carbohydrate content, this alpha2 allotype differs from the alpha1 chain in only 14 amino-acid positions; all of these are identical to the A2m(2) allotype of the alpha2 chain and confer subclass (or isotypic) character on the alpha2 chains. However, the A2m(2) allotype differs in six positions where A2m(1) and alpha1 are identical; the first two are just before the hinge and the other four are in the last (C(H)3) domain. The A2m allotypic character of alpha2 chains is attributed to several conformational factors in the sequence at positions 211-221, just before the hinge. The isoallotypic determinant shared by alpha1 chains and the A2m(1) allotype of alpha2 resides in the identity of their C(H)3 domains. Thus, the A2m(1) allotype appears to be a hybrid chain that is identical with alpha1 in the C(H)3 domain and identical with the A2m(2) alpha2 chain in the C(H)1 and C(H)2 domains and in the hinge, except for the allotypic determinants arising from four structural differences from residues 211-221. The genetic origin of isotypes, allotypes, and isoallotypes of the alpha chain has involved several events of homologous crossing over and neutral point mutations accumulated late in the evolutionary development of IgA immunoglobulins. Since the crossing over appears to occur between C(H)2 and C(H)3, heavy chain domains may be coded for by independent units in embryonic DNA that are analogous to the variable (V) and C segments of light-chain genes.
D000595:Amino Acid Sequence; D003434:Crossing Over, Genetic; D004220:Disulfides / Q000032:analysis; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D007126:Immunoglobulin Allotypes / Q000235:genetics; D009101:Multiple Myeloma / Q000276:immunology; D009154:Mutation; D011995:Recombination, Genetic
D004220:Disulfides; D007070:Immunoglobulin A; D007126:Immunoglobulin Allotypes