As CD4 T cells control the activation of B cells, macrophages, and, in some cases, CD8 T cells, the activation of naive CD4T cells by antigen may be the most important event in the initiation of adaptive immunity. It is now widely believed that naive CD4 Tcells require two distinct signals to proliferate and subsequently differentiate into the armed effector cells that mediate adaptive immunity (Schwartz, 1992). One of these signals determines which CD4 T cells will respond to a particular antigen; it is delivered by the receptor for antigen on the T cell (TCR), which it recognizes in the form of peptide fragments bound to major histocompatiblity complex (MHC) class II molecules (see Germain, 1994 [this issue of Cc//j). The T cell receptor is a multichain complex of proteins, and we shall later examine it in more detail (see also Weiss, 1994 [this issue of Cc/Q. The second signal, which is not delivered via the TCR and is not antigen specific, has been termed a costimulatory signal because, while essential, it does not by itself induce any response in T cells. However, when aTcell has its receptor lilgated and receives a costimulatory signal, the T cell will proliferate and differentiate into an armed effector cell. Moreover, T cells that bind antigen but do not receive a costimulatory signal are thought to die (Webb et al., 1990)