IDIOTYPIC DIVERSITY AND VARIABLE REGION GENE USAGE BY MOUSE ANTI-HLA-DQ3 MAB

The anti-HLA-DQ3 monoclonal antibodies (mAb) KS13, SO1, SO2, SO3, SO4, and SO5 recognize spatially close but distinct antigenic determinants , since they crossinhibit each other in their binding to HLA-DQ3 antig ens, but do not share idiotopes recognized in their antigen combining site by syngeneic and anti-id antisera and mAb. Furthermore, mAb SO1, SO3, SO4, and SO5 react also with HLA-DQ allospecificities other than HLA-DQ3. Sequence analysis of the heavy (V-H) and light (V-L) chain va riable region of the six mAb revealed preferential usage of V-H 36-60 and V-K 12/13 gene families. However, the individual V-H and V-L germl ine gene usage by the six mAb is diverse and the utilization of D, J(H ), and J(L) gene segments is heterogeneous. The diverse usage of V-H a nd V-L. gene segments and heterogeneous amino acid sequences of V-H an d V-L CDR, together with the heterogeneous idiotypic profile, may refl ect the complexity of the determinants recognized by the six mAb on HL A-DQ3 antigens. The results we have presented provide for the first ti me information about the structural basis of the diversity of antibodi es recognizing human histocompatibility antigens.