Antigen competition in cytotoxic T cell response to minor histocompatibility antigens.

Two populations of class-I-restricted CTL are generated from BDF1 mice against multiple minor-HA when BALB.B cells carrying multiple minor-HA are used as immunogen, whereas one population of Db-restricted CTL is generated when H-25.3 antigen on B6.C-H-25c cells is used as antigen. CTL generated against H-25.3 antigen on B6.C-H-25c cells are cytolytic to B6.C-H-25c and BALB.B targets, whereas CTL generated in the same manner with multiple minor-HA on BALB.B cells kill BALB.B targets only. This must be an instance of antigen competition, because H-25.3 antigen is immunostimulatory when used on its own, but not when accompanied by other minor-HA. This competition effect is not an artefact seen during the generation of CTL in MLC cultures in vitro, because it is also seen during the generation of CTL in vivo. We have not identified the immunodominant antigen(s) on BALB.B cells. We have studied this form of antigen competition in some detail. First, BDF1 spleen primed in vivo to multiple minor-HA on BALB.B cells do not respond in vitro to restimulation by H-25.3 antigen, suggesting that antigen competition is not mediated by suppressor cells, but that BALB.B cells do not prime BDF1 spleen cells against H-25.3 antigen in vivo. Second, BDF1 spleen cells primed to the same multiple minor-HA carried on F1(BALB/c X B6.C-H-25c) cells respond to restimulation by H-25.3 antigen in vitro. Third, BDF1 spleen cells primed in vivo to H-25.3 antigen on B6.C-H-25c cells do not respond in vitro to restimulation by multiple minor-HA on BALB.B cells, but they do respond to F1(BALB/c X B6.C-H-25c) cells that carry the same multiple minor-HA as BALB.B cells, and generate Db-restricted anti-H-25.3 CTL. Fourth, BDF1 spleen cells primed in vivo and boosted in vitro with B6.C-H-25c cells readily develop CTL to H-25.3 antigen, whereas when the BDF1 mice are exposed to H-25.3 antigen in vivo by repeated footpad injections of B6.C-H-25c cells, CTL to H-25.3 antigen do not develop. However, anti-H-25.3 CTL do develop after H-25.3 antigen-bearing B6.C-H-25c cells and antigen-specific Th cells are injected into preprimed BDF1 mice. These results are discussed with respect to possible mechanisms of antigen competition.