Mechanisms of induction of primary virus‐specific cytotoxic T lymphocyte responses

We have investigated the ability of various antigen‐presenting cell (APC) types to induce primary anti‐viral cytotoxic T lymphocyte (CTL) responses by single in vitro stimulation. Of these APC types, only dendritic cells (DC) and RMA‐S lymphoma cells could induce primary CTL responses, but by divergent mechanisms. DC were capable of generating primary virus‐specific CTL, either by presenting viral peptide or processed infectious virus. In contrast, RMA‐S cells could not present endogenous antigen, e. g. after virus infection, but this cell line very efficiently presented exogenous viral peptides to induce primary virus‐specific CTL in vitro. Spleen cells, lipopolysaccharide‐induced B cell blasts or the non‐mutated RMA cells did not have the ability to trigger unprimed T cells by single in vitro stimulation. We have investigated several characteristics important for primary CTL response induction by DC and RMA‐S cells (summarized in Fig. 6). Primary CTL response induction by DC or RMA‐S cells was blocked by anti‐LFA‐1 or anti‐CD8 monoclonal antibodies (mAb). DC rapidly aggregated with unprimed T cells, which was independent of LFA‐1 and CD8 molecules. RMA‐S cells did not form conjugates with unprimed T cells. Despite their abundant major histocompatibility complex (MHC) class I cell‐surface expression, DC did not bind much exogenously added viral peptide. In contrast, the MHC class I molecules on RMA‐S cells bound a large quantity of exogenously administered peptide. Powerful adhesion by DC and high expression of relevant MHC/peptide complexes on RMA‐S cells are important features in the initial contact with unprimed T lymphocytes. In a later stage of contact, both DC and RMA‐S cells activate LFA‐1 (and CD8) molecules at the T cell surface to strengthen and maintain the contact between T cell and APC.