[Analysis of VH genes which encode the variable region of monoclonal antibodies directed to cancer-associated carbohydrate antigens].

Immune responses against cancer-associated, carbohydrate antigens are investigated by studying idiotypic determinants of specific antibodies with monoclonal anti-idiotypic antibodies, and by analyzing the structure of VH genes which encode the V region of the anti-carbohydrate antibodies. Four syngenic anti-idiotypic antibodies towards monoclonal antibodies which are specific to the sialyl Lewis A antigen and two kinds of SSEA-1 related antigens (sialyl SSEA-1 and fucosul SSEA-1) were obtained. Antibodies directed to carbohydrate antigens were mostly of IgM isotype, indicating these antigens are T-independent antigens, while anti-idiotypic monoclonal antibodies directed to those antibodies were mostly of IgG isotype, suggesting that T cells participate actively in the anti-idiotypic response. The Northern blotting analysis of VH genes of monoclonal antibodies directed to negatively-charged carbohydrate antigens such as gangliosides or sulfated glycolipids expressed the VH gene family J558 (group 1), followed by J606 (group 6) and Q52 (group 2) families. On the other hand, monoclonal antibodies directed to SSEA-1 related neutral carbohydrate antigens expressed VH genes of a minor family such as X24 (group 4), V31 (group 9), or 7183 (group 5). The same VH family as expressed in anti-SSEA-1 antibody (x24) was also expressed in the antibodies such as anti-i and anti-I antibodies, which are directed to the synthetic precursors of the SSEA-1 antigen. In either case, the antibodies directed to one particular carbohydrate antigen tended to express the VH gene of one particular family exclusively. This suggests idiotypic homogeneity of the anti-carbohydrate antibodies.