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T-cell receptor

The T cell receptor (TCR) is a heterodimeric protein complex anchored on the T cells’ surface. TCRs consist of two polypeptides attached to the cell membrane, forming the antigen recognition or binding site. Based on their polypeptide composition, there are two TCRs: highly variable alpha and beta, or gamma and delta chains. Most T cells (~95%) express the alpha-beta pair and specifically recognize processed peptides presented through Major Histocompatibility Complex (MHC) class I and II proteins. About 5% of T cells express the gamma-delta chain pair and recognize unprocessed antigens. TCR polypeptides are each associated non-covalently with CD3 proteins, which are necessary for intracellular signal transduction.

“Chimeric antigen receptor (CAR) and T-cell receptor (TCR) engineered T cells. CAR-T cells usually target surface antigens, whereas TCR-T cells recognize internally processed proteins presented by molecules of the major histocompatibility complex (MHC) as peptide-MHC (pMHC) complexes. Each TCR is specific for a pMHC, allowing an infinite set of pMHC combinations that can be exploited for TCR-T-cell therapy. Created with BioRender.com (San Francisco, CA, USA).”

T cells, through TCR engagement, play a critical role in adaptive immune responses by recognizing antigens derived from microorganisms and tumor cells (e.g., neoantigen peptides). One modality in cancer immunotherapy relies on engineered TCRs to target specific tumor antigens. Adoptive T cell therapies, where autologous T cells are modified to express engineered tumor-antigen specific TCRs (TCR-T cells), have been very effective in treating melanoma and other solid tumors.

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