Genetics of the antibody response to an endothelial transplantation antigen in the rat

Abstract

Immunization of MAXX (RTI n) rats with pooled spleen and lymph node cells from the BN (RTI n) strain results in the formation of alloantibodies against a nonmajor histocompatibility complex (MHC) encoded transplantation antigen on peritubular capillary and venous endothelium of the kidney. Since ACI (RTI a) strain animals did not respond to the antigen, the genetics of the in vivo humoral immune response to repeated immunization were investigated in 43 animals of the second filial generation from the responder MAXX and the nonresponder ACI strain, as well as in 13 animals produced by backcrossing (MAXX x ACI)FI and ACI. Because 38/40 RTI n-positive animals responded, while 16/16 RTI a/a recipients did not, it was shown that the RTI n haplotype was required for responsiveness. Using the intra-MHC recombinant strains DA.1I (RTI.A nB aD aE u and WRC (RTI.A nB nD a), the immune response was mapped within the class II region of the MHC-complex. Effects of MHC-(in)compatibility between donor and recipient on the response were ruled out, since MAXX rats formed endothelial antibodies upon immunization with the MHC-incompatible BN.1L (RT1 1, BN.1A (RTI a), and WKY (RTI k) cells, whereas ACI animals failed to produce endothelial antibodies after immunization with BN.1A cells. Furthermore, the response appears to be thymus dependent because congenitally athymic WAG/rnu (RTI u) rats failed to produce endothelial antibodies, in contrast to the euthymic WAG/Rij (RT1 u) strain.