These studies present a model for T-T collaboration for the generation of cytotoxic T lymphocytes. The in vitro CTL response against Qa-1 alloantigens in B6 Qa-1 congenic mice requires that animals are first primed in vivo with Qa-1 together with a second (helper) antigen. Both the antigen recognized by CTL (Qa-1) and Th (H-Y) must be presented on the same APC for successful priming. This findings is consistent with a linked recognition model whereby both molecules are presented on the same APC in order to accomplish close proximity between the two T cells. To further test this model, we demonstrated that in the absence of the helper antigen, H-Y, mice could be successfully primed against Qa-1 if coinoculated with a product of a Th, IL-2. We further showed that mice treated with anti-L3T4 antibodies could not be primed to Qa-1 even though the cells used for immunization expressed the H-Y helper antigen. Taken together, these results lend further support to a model of linked recognition between Th and CTL.P where close proximity allows for the lymphokine IL-2 to bind to its receptor on the CTL allowing for the successful induction of CTL.P.