APC antigen presentation to naive CD4⁺ cell.

(1) APCs presenting antigens on MHC class II molecules (signal 1) are stimulated to express costimulatory molecules (signal 2) by endogenous and exogenous factors (signal 0) → naive T cells receiving signal 1 in the presence of signal 2 are activated and an immune response is initiated against the antigen. (2) An APC presenting antigen (signal 1) and stimulated by signal 0 to express costimulation (signal 2) does not find a T-cell receptor (and thus a naive T cell) capable of recognizing the presented antigen → T cell previously deleted or down-regulated (anergy) when encountering the same (or similar) antigen without signal 2. (3) A naive T cell receiving signal 1 in the absence of signal 2, by an APC, is deleted or anergy is induced.