Differences in TCRs and CARs
| . | TCR . | CAR . |
|---|---|---|
| Target | Intracellular antigen (recognition of peptide/HLA complex), HLA restricted | Surface antigen (conventionally, not always) |
| Intracellular signaling domains | Formation of CD3ελ, CD3εδ heterodimers, and CD3ζ homodimer, 10 ITAMs | Conventionally some combination of linked CD28 or 4-1BB and CD3ζ, 3 ITAMs |
| Coreceptor requirement | Yes (CD4, CD8) | Not required |
| Activation threshold | 1-3 molecules on target cell24,25 | >100 molecules on target cell26 |
| Sensitivity | Higher antigen sensitivity27-29 | Lower antigen sensitivity,27-29 up to 100-fold less at low-antigen levels30,31 |
| Affinity | Generally lower (allowing for serial triggering),32 in the mM range | Slightly higher,33 in the nM range |
| Immune synapse formation | Highly organized, 5-10 min formation time34 | Disorganized, <2 min formation time34 |
| Downstream activation/phosphorylation | Stronger activation28 | Weaker activation28 |
| . | TCR . | CAR . |
|---|---|---|
| Target | Intracellular antigen (recognition of peptide/HLA complex), HLA restricted | Surface antigen (conventionally, not always) |
| Intracellular signaling domains | Formation of CD3ελ, CD3εδ heterodimers, and CD3ζ homodimer, 10 ITAMs | Conventionally some combination of linked CD28 or 4-1BB and CD3ζ, 3 ITAMs |
| Coreceptor requirement | Yes (CD4, CD8) | Not required |
| Activation threshold | 1-3 molecules on target cell24,25 | >100 molecules on target cell26 |
| Sensitivity | Higher antigen sensitivity27-29 | Lower antigen sensitivity,27-29 up to 100-fold less at low-antigen levels30,31 |
| Affinity | Generally lower (allowing for serial triggering),32 in the mM range | Slightly higher,33 in the nM range |
| Immune synapse formation | Highly organized, 5-10 min formation time34 | Disorganized, <2 min formation time34 |
| Downstream activation/phosphorylation | Stronger activation28 | Weaker activation28 |
ITAMs, immunoreceptor tyrosine-based activation motifs.