T lymphocytes, specifically CD4+ T cells, are considered the leaders of the adaptive immune response to protein antigens. These naive, undifferentiated T cells live in the lymphoid tissues (e.g., lymph nodes, spleen) and must produce effector T cells that may be “summoned” to the tumor site. T-cell receptors (TCRs) are formed when DNA recombines during T cell development and are expressed on the surface of naive T cells. These TCRs enable naive T cells to identify peptide antigens that are bound to major histocompatibility complex (MHC) molecules on antigen-presenting cells (APCs). This is the first of two required signals for T cell activation. The second signal comes from the recruitment of co-stimulators. A common co-stimulator is the CD28 receptor and B7 molecules. Other TCRs include CTLA-4, ICOS and PD-1 with ligands homologous to the B7 proteins. After initial T cell activation, expression of costimulatory and coinhibitory molecules will positively or negatively control the growth, differentiation and function of T cell response. Immune checkpoints, including CTLA-4 and PD-1, are regulators that maintain homeostasis, prevent autoimmunity and have the potential to aid in tumor immune evasion.
T cell activiation and regulation of response.
Immune checkpoint regulation pathways.
Thank you for participating in this module. Click below to download the certificate.