Allotypic and isotypic aspects of human immunoglobulin A.

The location of isotypic, isoallotypic and allotypic determinants is reviewed in the light of data obtained when specific antisera are tested with proteolytic fragments of IgA molecules or mutants of IgA obtained from patients with alpha-heavy chain disease. Isotypic determinants are distributed throughout the alpha chain constant regions although when intact IgA proteins are used as immunogens the CH3 domain is immunodominant. Alpha 1 subclass specific isotypic determinants are present in both Fab and Fc fragments. Amino acid sequence analysis suggest that alpha 1 subclass isotypic determinants depend on substitution in the CH1, hinge and/or CH2 domain. The isoallotypic determinants nA2m(2) appears to be located on the CH1 domain and appears to require disulphide-linked alpha chains for its expression. The allotypic determinant A2m(2) appears to be located in the CH3 domain involving residues 428, 458 and/or 467. The latter residues are present in both A2m(1) and A1 proteins which indicates that for A2m(1) to be the antithetical determinant of A2m(2), the determinant formed by residues 428, 458 and/or 467 in these proteins must be influenced by subclass differences which allows its expression in A2m(1) proteins and not in A1 proteins.