Syngeneic anti-idiotypes against monoclonal anti-HLA-DR antibodies: characterization of recurrent idiotopes.

Abstract

Monoclonal anti-HLA-DR antibody (anti-DR mAb) reactivity was investigated at the idiotypic level; three syngeneic anti-idiotype (Id) sera were raised against three monomorphic anti-DR mAb (206, BM 50, and D 1.12). The syngeneic anti-Id responses exhibited some differences in their intensity and the idiotypic determinants recognized by the three anti-Id sera were localized, at least in part, on the antigen combining site of the respective anti-DR mAb. Idiotype analysis of 24 anti-DR mAb was performed with these anti-Id sera by Id-binding inhibition assays. Idiotypic cross-reactivity was demonstrated for 12 out of the 24 anti-DR mAb, indicating a large degree of idiotypic recurrence. Analysis of the cross-inhibition patterns led us to define at least five sets of recurrent idiotopes: one set cross-reacting with anti-206 Id, the second with both anti-BM 50 and anti-D 1.12 Id, the third with anti-BM 50 Id only, the fourth with anti-D 1.12 Id only, and a fifth set was shared by D 1.12 and NE 4. Eleven monomorphic anti-DR mAb and one polymorphic anti-DR 3 mAb (16.23) did not cross-react with the three anti-Id sera. These results suggest that the mouse antibody response to monomorphic determinants on human Ia antigens is based on a limited number of recurrent idiotopes. In two cases, recurrent idiotopes could be related to a similar anti-DR mAb fine specificity. These anti-Id provide useful reagents to classify and compare anti-DR mAb.