Effector mechanism in rejection of allografts expressing an isolated minor histocompatibility disparity. Importance of cytotoxic T lymphocytes in the rejection of H-43a allografts by H-43b mice.

To explore effector mechanisms in allograft rejection, we transplanted skin grafts (SG) across a single minor histocompatibility locus (H-43) using mouse strains carrying the H-43b allele as SG recipients and those carrying the H-43a allele as SG donors. Recipients' spleen cells (SC) were assayed at various intervals for 200 days for anti-H-43a cytotoxic T lymphocyte (CTL) responsiveness, as well as delayed-type hypersensitivity (DTH) responsiveness. When H-43a SG from C3H.SW mice were transplanted to H-43b CWB mice, two thirds of the recipients rejected the SG, and recipients' SC showed marked self-H-2Kb-restricted anti-H-43a CTL responsiveness until the end of the observation period. In contrast,H-43aSG transplanted to H-43b (B10.BRxCWB)F1 (BWF1) mice survived in almost all of the BWF1 recipients. The anti-H-43a CTL responsiveness of the recipients' SC was evident until day 40 but thereafter started to wane and eventually disappeared. Notably, BWF1 mice whose self-H-2Kb-restricted anti-H-43a CTL precursors had been primed by prior injection with H-43a SC rejected H-2Kb-bearing H-43a CSW SG but not H-2k, H-43a C3H/HeN SG. In contrast, an anti-H-43a DTH response was not induced in any of the CWB and BWF1 recipients, including CWB recipients who rejected the H-43a SG. Since it has been well documented that anti-H-43a CTL are restricted solely by self-H-2Kb, the results in this study indicate that self-H-2Kb-restricted anti-H-43a CTL are responsible for rejection of H-43a allografts by H-43b recipient mice.