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. Author manuscript; available in PMC: 2016 Aug 1.
Published in final edited form as: Trends Immunol. 2015 Jul 11;36(8):494–502. doi: 10.1016/j.it.2015.06.004

Figure 1. Signaling of conventional and CAR T cells.

Figure 1

Left: Delivery of signals 1 and 2 to conventional T cells is initiated by the TCR interacting with pMHC on an APC. The spatial distance between the T cell and the APC is ~15nm, which physically excludes from the synapse the inhibitory receptor CD45 because of its large ectodomain. Interaction of CD4/CD8 co-receptors with MHC recruits Lck to the TCR complex, where it phosphorylates and activates Zap70, which provides signal 1. Ligation of the co-stimulatory receptor CD28 by CD80/CD86 results in PI3K activation and delivers signal 2 for full T cell activation. Right: Single receptor design showing a second-generation CAR containing CD3z and CD28 endodomains in cis. Activation of these CARs by a single tumor antigen is sufficient to deliver both signals 1 and 2 in cis, resulting in T cell activation. The spatial distance between CAR T cells and target tumor cells is not known, nor is it known whether this distance is small enough to physically exclude the phosphatase CD45 from the synapse. It is also unknown whether CARs interact with endogenous TCR/CD3z or CD4/CD8 co-receptors.