ALLOREACTIVE T-CELLS THAT DO NOT REQUIRE TCR AND CD8 COENGAGEMENT AREPRESENT IN NAIVE MICE AND CONTRIBUTE TO GRAFT-REJECTION

Class I alloreactive CTL populations have been defined as either CD8 d ependent or CD8 independent, based upon their ability to kill target c ells in the presence of Ab to CDS. The CDS-dependent population uses C DS in a coreceptor role with the TCR, and mutations in the class I mol ecule that destroy the CD8 binding site abrogate CTL killing, even if the target cell expresses other allelic forms of class I molecules wit h an intact binding site for CD8, The CD8-independent population appar ently does not require CDS, as Ab to CDS has no effect on the ability of these cells to kid appropriate target cells. We have isolated a thi rd population of CTL that is inhibited by the addition of CD8 Ab yet c an kill target cells that express the alloantigenic molecule incapable of binding CDS, provided that the target cells also express non antig enic class I molecules that contain an intact binding site for CD8. We refer to these cells as CDS bystander-dependent CTL. Many (10 of 12) of these CTL were able to kill H-2K(b)-expressing transfectants of T2 cells, consistent with the idea that they recognize a peptide-independ ent determinant that may be expressed at a high density on the cell su rface. These CDS bystander-dependent CTL are only readily detectable i n vitro when spleen cells from mice primed in vivo with a skin graft a re used.