Table 1.

Summary of similarities and differences between TCR and CAR.

		TCR	CAR
Structure	Receptor clustering	One pMHC potentially enough [18,19]	Clustering required [20,21,22]
	ITAM number	10 ITAMs provided by the CD3 complex [23]	Up to 3 ITAMs per CAR [23]
	Affinity/ Sensitivity	Lower affinity, higher sensitivity	Higher affinity [24], lower sensitivity [25]
	Phosph. of CD3 subunits	Phosph. of CD3 ζ, γ, δ, ε [26]	Phosph. of only CD3 ζ [25]
Signaling	Phosph. of signaling molecules	Stronger phosph. of ZAP-70, ITAMs and PLCγ1 than in CAR [27,28]	Stronger phosph. of Lck and ERK than in TCR [29]
	Recruitment of signaling molecules	More efficient recruitment of ZAP-70, CD2 and LFA-1 than in CAR [27,28]	Less dependent on LFA-1:ICAM-1 interaction and LAT [21,25,29]
	Upon increased antigen exposure	Maintain an earlier differentiation phenotype upon strong stimulation [30]	Higher levels of co-inhibitory molecules upon activation [30]
	IS structure	Classical “bull’s eye” structure [29] or multifocal structures formed by Th2 cells [31] or at the interface with DCs [32]	Non-classical, disorganized IS with multifocal pattern [29]
Immunological Synapse	SMACs	Conventional IS consisting of cSMAC, pSMAC and dSMAC [33]	Merged cSMAC and pSMAC, no adhesion molecule ring [21,29]
	Lck	One central Lck cluster [29]	Disorganized Lck patches [29]
	Duration	Usually slower/weaker effector function [29,30]; longer IS duration, slower off-rate from target [29]	Faster cytotoxic granule secretion and faster resolution of IS [29]
	Resting state	Constitutive internalization of TCR complex through clathrin-dependent endocytosis (CDE) [34]	Unknown
Trafficking	Upon activation	Engaged TCRs: Clathrin- independent endocytosis (CIE) for internalization, recycling or lysosomal degradation [34,35] Bystander TCRs: CDE for internalization and recycling [34,35]	Engagement of antigens induced rapid lysosomal ubiquitination [36] High-affinity CAR T cells demonstrated enhanced trogocytosis [37]