Figure 1 CTLA-4 and PD-1–PD-L1 immune checkpoints Figure 1 | CTLA-4 and PD-1–PD-L1 immune checkpoints. a | APCs present peptides comprising 8–9 amino acid residues in the context of MHC I molecules, which can interact with and promote signalling by TCRs on the surface of CD8+ cytotoxic T cells within lymph nodes. APCs can also present peptides of 14–21 amino acid residues bound to MHC II molecules to CD4+ T-helper cells. T-cell activation upon TCR signalling requires co-stimulatory signals transmitted via CD28, which is activated by binding to B7-1 and/or B7-2 molecules that are also presented on the surface of APCs; however, the CTLA-4 checkpoint protein is also expressed by T cells, and competes with CD28 for binding to B7-1 and/or B7-2, and interaction of CTLA-4 with B7-1 or B7-2 results in inhibitory signalling, T-cell anergy and apoptosis. b | Activated CD8+ cytotoxic T cells can recognize their target antigen peptide/MHC I complexes presented on tumour cells and initiate tumour-cell lysis. Tumour cells can express PD-L1 and/or PD-L2 that bind to PD-1 on T cells, resulting in inhibitory checkpoint signalling that decreases cytotoxicity and leads to T-cell exhaustion. PD-1-blocking antibodies inhibit the interaction of PD-L1 and PD-L2 with PD-1, resulting in enhanced T-cell cytotoxicity, increased cytokine production, and ultimately tumour-cell lysis. Anti-PD-L1 antibodies can have similar effects on T cells, but only inhibit the interaction between PD-L1 and PD-1. APC, antigen-presenting cell; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; IL-2, interleukin 2; MHC I, major histocompatibility complex class I; MHC II, major histocompatibility complex class II; PD-1, programmed cell-death protein 1; PD-L1, programmed cell death 1 ligand 1; PD-L2, programmed cell death 1 ligand 2; TCR, T-cell receptor. Goodman, A. et al. (2016) PD‑1–PD‑L1 immune-checkpoint blockade in B‑cell lymphomas Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2016.168