No abstract

We have reviewed evidence for the hypothesis that T-cell activation by antigen is an all or none process which is triggered when signal strength exceeds a certain threshold. Signal is generated by multivalent interaction between T-cell antigen receptors (TCR) and antigenic epitopes on the surface of antigen-presenting cells (APC) or target cells. Therefore total signal strength (Stot) will depend upon the concentration of TCR (and other accessory molecules that bind to cell surface ligands, e.g. CD4 and CD8) on T cells, the concentration of antigen on APC or targets and the affinity of interaction between receptors (a broad term incorporating TCR plus CD4 and CD8) and antigen. This hypothesis means that T-cell self tolerance is quantitatively determined by self-antigen concentrations on cell surfaces. Implications for a variety of immunological phenomenona are reviewed.

SUMMARYA cytotoxic response to murine cytomegalovirus (MCMV) was obtained by the culture of lymph node cells from mice inoculated with MCMV into both hind footpads 7 days previously. The cytotoxicity was mediated by Thy1.2 +, Lyt2 +, H-2-restricted effector cells and was virus-specific. Investigation of the in vitro conditions established that T cell proliferation was necessary for optimal generation of cytotoxicity, that proliferation was dependent upon Thyl.2 +, Lyt2 + cell populations and that supernatants from concanavalin A-activated spleen cells enhanced the levels of cytotoxicity obtained.

Summary. The preparation of target celts susceptible to lysis by murine c>'tomegalovirus (MCMV)-immune T cells in vitro was investigated and found to be dependeni upon target cell type, culture conditions, virus adsorption proiocol and virus preparation. Optimally sensitive MCMV-infected targeis were obtained by preculturc of mouse embryo fibroblasts (Mth) in 3"/o vol/vol concanavalin-A-stimu!ated spleen cell supernatant (CSS)-supplemenied medium, adsorption of salivary gland stock MCMV under 800 g centrifugation atid at least 4 h furlher incubation at 37' before addition of T cells. In conirast, salivary gland stock MCMV did tiot cau,se thioglycollate-induced peritoneal exudaic cells lo be susceptible to MCMVspecific T cell-mediated lysis, whereas tissue culiure-passaged stock MCMV was successful. The preparation of MCMV-infecied target cells is discussed in terms of the need for H-2 and viral antigen expression for T cell recognition.