Introduction:
T cells are immune cells capable of responding to intracellular antigens, for example, dervied from infections or cancerous mutations. T-cell antigen recognition relies on a T-cell receptor (TCR) that recognises a peptide presented by a major histocompatibility complex (pMHC) on the surface of the antigen-presenting cells. This recognition is primarily driven by Major Histocompatbility Complex class I (MHC-I) surface expression and CD8+ T cells expressing a TCR that can recognise the given pMHC complex; this identification of TCRs for therapeutic use is driven by selection of therapeutically relevant T-cell populations from patients, or driving the expansion of a T-cell population from the naive repertoire towards a given antigen in healthy donors. (Jenkins, “De novo designed pMHC binders facilitate T cell induced killing of cancer cells”)
Types of T cells:
Alpha Beta T cells: Most T cells express the alpha beta TCR (T cell receptor) protein and have a helper (CD4+) or cytotoxic (CD8+) phenotype.
NK T cell: A subset of cytotoxic T cell also express NK associated antigens and have been called “NK-like” T-cells. They are not NK cells which are a type of lymphocyte related to T cells that act less specifically and attack cancer cells and virus infected cells.
Gamma delta (γδ) T cells: are a specialized subset of T lymphocytes, characterized by their unique T cell receptor (TCR) composed of γ and δ chains. Unlike the more common αβ T cells, γδ T cells recognize a broader range of antigens, including those not presented by MHC molecules, and play a crucial role in both innate and adaptive immunity. They are found in various tissues, particularly in epithelial and mucosal layers, and contribute to immune surveillance, tissue homeostasis, and inflammation.
A small population of T cells express the gamma delta TCR and usually have a double negative (CD-CD8-) phenotype, although some may express CD8 or more rarely, CD4. Normal gamma delta T cells are preferentially located at the extranodal sites such as the splenic red pulp, gastrointestinal tract, and skin.
–Vgamma9Vdelta2 T cells: are the largest gama delta T cell subpopulation in healthy adults. They are naturally occurring cells int he human immune system that are endowed with a tumor recognition mechanism, allowing them to specifically recognize and kill cells under stress, such as cancerous cells, while leaving healthy cells unharmed. They have properties of both the innate and adaptive immune systems, enabling them to serve as a functional bridge between these two critical systems to impact tumor killing. They exist as Tumor-infiltrating lymphoctyes (TILs) in many different cancer indications.
Regulation of T cells:
Programmed death receptor-1 (PD-1) is a protein found on T cells that acts as a “brake” on the immune system, preventing T cells from overreacting and attacking other cells, including those that may be fighting cancer. When PD-1 binds to its partner protein, PD-L1, it suppresses T cell activity, helping to regulate immune responses and prevent autoimmune diseases.