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CTLA4

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4 or CTLA-4), also named as cluster of differentiation 152 (CD152), is a protein receptor that, working as an immune checkpoint, downregulates immune responses. On account of the ability to stop potentially autoreactive T cells at the initial stage of naive T-cell activation, usually in lymph nodes, CTLA4 is regarded as the "leader" of the immune checkpoint inhibitors. It is a CD28 homolog with a much higher binding affinity for B7, while, different from CD28, binding of CTLA4 to B7 does not generate a stimulatory signal. In this case, this competitive binding enables to prevent the costimulatory signal normally gave by CD28:B7 binding.
Besides, some studies have proven that CTLA4 binding to B7 may actually form inhibitory signals that counteract the stimulatory signals from CD28:B7 and TCR:MHC binding. There exist some possible mechanisms for such inhibitory signals: inhibition of CD28 or its signaling pathway, direct inhibition at the TCR immune synapse, or improved mobility of T cells causing induced ability to interact with APCs. Additionally, CTLA4 itself is subject to regulation, particularly by localization within the cell. In resting naive T cells it is located mainly in the intracellular compartment. And it is found to expressed in head and neck cancer.
Gene ID: 1493
UniProt ID: P16410