PROLIFERATION AND MHC UNRESTRICTED BYSTANDER LYSIS BY VIRUS-SPECIFIC CYTOTOXIC T-CELLS FOLLOWING ANTIGEN SELF-PRESENTATION

Cytotoxic T cells (CTL) not only act as effector cells, but can also s erve as antigen-presenting cells (APC) for other CTL due to their expr ession of major histocompatibility complex (MHC) class I molecules. In the present study we show that independently derived CTL lines (CTLL) with specificity for an L-d-presented nonapeptide corresponding to am ino acids 168-176 of the immediate-early 1 (IE1) protein of murine cyt omegalovirus not only lyse syngeneic but also allogeneic target cells, if the peptide is present during the cytolytic assay. Whereas a short peptide pulse is sufficient to render syngeneic cells susceptible to lysis, continued presence of soluble peptide is mandatory for the lysi s of allogeneic target cells. This indicates a difference in the mecha nisms involved. Syngeneic BALB/c B cell blasts ((KDLd)-D-d-L-d) and mu tant BALB/c-H-2(dm2) B cell blasts lacking the restricting Ld molecule s ((KDO)-D-d-O-d) were lysed to a similar extent in the absence of the IE1 nonapeptide, provided that the IE1-specific CTL had been pre-incu bated with the peptide before the cytolytic assay. Since the mutant ce lls cannot present the IE1 peptide, their lysis indicates an MHC-unres tricted, peptide-independent mode of recognition by the CTLL. In addit ion, proliferation of the CTLL takes place after incubation with the c ognate peptide, even in the absence of professional APC. These data in dicate inter-CTL antigen self-presentation, resulting in activation of the lytic machinery leading to peptide-independent bystander lysis of allogeneic as well as syngeneic target cells.