Antigen recognition by T cells: Quantitative effects of augmentation by antibodies providing accessory interactions

Although engagement of the TCR via antibody can be sufficient to trigger T cells, responses to Ag-bearing cells require additional "accessory" interactions in many cases. A method has been developed which allows preparation of surfaces bearing both purified class I alloantigen and coimmobilized antibodies. With this approach, it is possible to mimic such "accessory" interactions and to examine their quantitative effects on triggering via TCR-Ag interaction. Experiments are described which use this approach to examine triggering of degranulation by cloned, allogeneic CTL lines. Coimmobilization of antibodies specific for any of a variety of CTL surface proteins, including CD8, class I MHC proteins, CD45 (T200) and Thy-1, had the effect of decreasing the critical threshold density of Ag necessary to trigger responses, and decreasing by an order of magnitude the density required to stimulate a half-maximal response. Furthermore, in comparison with the 30-min lag seen with Ag alone, response was initiated immediately when an antibody specific for a CTL surface component was present. These results are consistent with the hypothesis that any CTL surface molecule having sufficient affinity for a component of the target surface can contribute to activation via the Ag-specific TCR; and at low Ag density could determine whether any response occurs.