Programmed Cell Death of T Cells Signaled by the T Cell Receptor and the $\alpha_3$ Domain of Class I MHC

• Published in: Science (American Association for the Advancement of Science) 1991-06, Vol.252 (5011), p.1424-1427
• Main Authors: Sambhara, Suryaprakash R., Miller, Richard G.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antigen receptors, T cell; Antigens, Differentiation, T-Lymphocyte - physiology; Apoptosis; CD8 Antigens; Cell death; Cell lines; Cell Survival - physiology; Cells, Cultured; Cultured cells; Histocompatibility Antigens Class I - physiology; Immune response; In Vitro Techniques; Interleukin-2 - analysis; Lymphocyte Culture Test, Mixed; Lymphocytes; Major histocompatibility complex; Mice; Molecules; Receptors; Receptors, Antigen, T-Cell - physiology; Signal Transduction; Spleen cells; T cell antigen receptors; T cells; T lymphocytes; T-Lymphocytes - physiology; T-Lymphocytes, Cytotoxic - physiology; Transponders
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1828618

As well as being activated or rendered unresponsive, mature T lymphocytes can be deleted, depending on the signals received by the cell. Deletion by programmed cell death (apoptosis) is triggered if a T cell that has received a signal through its T cell receptor complex also receives a signal through the ~$\alpha_3$ domain of its class I major histocompatibility complex (MHC) molecule. Such a signal can be delivered by a CD8 molecule, which recognizes the $\alpha_3$ domain, or by an antibody to this domain. Precursors of both cytotoxic T lymphocytes (CTL's) and T helper cells are sensitive to this signal but become resistant at some point before completing differentiation into functioning CTL's or T helper cells. Because CTL's carry CD8, they can induce ceU death in T cells that recognize them. This pathway may be important in both removal of autoreactive T cells and immunoregulation.