MONOCLONAL ANTI-Ia MURINE ALLOANTIBODIES CROSSREACTIVE WITH THE Ia-HOMOLOGUES OF OTHER MAMMALIAN SPECIES INCLUDING HUMANS1

Abstract

Two murine monoclonal anti-Ia alloantibodies (ISCR2 and ISCR3) crossreactive with lymphocytes of other mammalian species including humans have been established. These hybridomas were derived from A.TH mice immunized with A.TL lymphocytes, and they reacted with murine Ia antigens, as judged by complement-dependent cytotoxicity assays and chemical analysis. Genetic mapping analysis suggested that ISCR2 recognizes the allotypic determinants shared between theI-Aand theI-Emolecules. On the other hand, the specificity of ISCR3 was shown to correspond to the serological specificity Ia.7 and directed to theI-Esubregion gene product (Eα). The genetic specificity of ISCR3 was also confirmed by sequential precipitatin analysis performed on the internally labeled B10.BR spleen cell antigen. These antibodies showed interspecies crossreactions with nonmurine lymphocytes. ISCR2 showed reactivity on human and dog lymphoytes, but not with rat lymphocytes. ISCR3 reacted with human, dog, and rat lymphocytes but not with chicken or frog lymphocytes. Furthermore, ISCR3 was shown to be capable of eliminating a population of cells neccessary for induction of human allogeneic killer cells in vitro. Treatment of stimulator cells with ISCR3 and complement drastically reduced the induction of the killer activity.