Idiotypic diversity and variable region gene usage by mouse anti-HLA-DQ3 mAb

Abstract

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 antigens, 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 (VH) and light (VL) chain variable region of the six mAb revealed preferential usage of VH 36-60 and VK 12/13 gene families. However, the individual VH and VL germline gene usage by the six mAb is diverse and the utilization of D, JH, and JL gene segments is heterogeneous. The diverse usage of VH and VL gene segments and heterogeneous amino acid sequences of VH and VL CDR, together with the heterogeneous idiotypic profile, may reflect the complexity of the determinants recognized by the six mAb on HLA-DQ3 antigens. The results we have presented provide for the first time information about the structural basis of the diversity of antibodies recognizing human histocompatibility antigens.