Cosegregation of the polymorphic C4 with the MHC in the frog, Xenopus laevis.

Employing isoeletric focusing combined with enzyme-linked immunoelectrotransfer blot analysis, the fourth component of complement (C4) was analyzed in the two highly histocompatible, major histocompatibility complex homozygous groups (J and K) of Xenopus laevis. Each group had a characteristic C4 isoelectric focusing pattern, i.e., an isoelectric point range of 8.0-8.5 for J (C4jC4j) and 7.6-8.1 for K (C4kC4k). In (J X K)F1 frogs, C4 proteins were expressed in a codominant fashion (C4jC4k). In the backcrossed progeny B1 [J X (J X K)F1], those with C4jC4j rejected (J X K)F1 skins hyperacutely (less than 17 days), were high responders against (J X K)F1 cells, and nonstimulators to J cells in mixed lymphocyte reaction (MLR), but they did not suffer from the graft-versus-host reaction (GVHR), even after the injection of (J X K)F1 cell-stimulated J splenocytes. On the other hand, the B1 frogs with C4jC4k acutely or chronically (greater than 17 days) rejected (J X K)F1 skins, were low or nonresponders against (J X K)F1 cells and high stimulators to J cells in MLR, and they suffered from GVHR after the injection of prestimulated J splenocytes. These results argue for the notion that the genes equivalent to mammalian class III map to the MHC at the phylogenetic level of the anuran amphibian.