Molecular biology and immunology for clinicians, 12: T-cell co-stimulatory molecules

T-cells are activated by their interaction with antigen-presenting cells. Antigen-presenting cells process and then express peptide fragments of the target protein in a complex with self-proteins known as major histocompatibility complex (MHC) proteins on the antigen-presenting cells' surface. However, the interaction of T-cell with antigen on the antigen-presenting cell is not sufficient to elicit T-cell activation. The T-cell must receive a second signal from the antigen-presenting cell. These "co-stimulatory signals" are mediated by other proteins on the antigen-presenting cell surface that interact with T-cell surface proteins other than the antigen receptor, the protein complex receiving the peptide fragment's specific antigen signal. Some of these co-stimulatory proteins are constitutively expressed, some are up-regulated during an immune response; some interactions stimulate activation, some suppress it. Thus, these receptor-ligand protein pairs represent new sites for blockade of immune responses in immunologically-mediated diseases, like rheumatoid arthritis, lupus, and transplant graft rejection.