Killer cells reactive to altered-self antigens can also be alloreactive.

Murine cytotoxic thymus-derived lymphocytes immunized against cells bearing foreign minor histocompatibility antigens are specific for the immunizing minor antigens and for their own major H-2 antigens; they do not lyse target cells that bear the correct minor antigens plus a different H-2 haplotype. These are referred to as "altered-self" or "self-plus-X" killer cells. Alloreactive killer cells are those which respond to allogeneic cells expressing a foreign (non-self) H-2 haplotype. In this study, cytotoxic lymphocytes were immunized against minor histocompatibility differences in vivo and in vitro. These effector cells killed the immunizing altered-self target very well and showed about 1% cross-reactive lysis of an allogeneic target differing from themselves only at H-2. These cross-reactive clones were then selected for by repeated in vitro stimulation with the cells bearing foreign H-2 such that an effector population was obtained which lysed both the altered-self and the alloreactive target with the same efficiency. Cold target competition experiments established that the same killer cell could lyse either target; however, it was not determined if a killer cell uses the same receptor to respond to altered-self antigens as it does respond to foreign H-2 antigens.