Lymphocyte Activation in Health and Disease

Critical Reviews in Immunology
M J Berridge

Abstract

Lymphocytes employ a complex assembly of signaling elements that have been organized on a spatiotemporal map to define their role in stimulating both proliferation and apoptosis. The antigen/major histocompatibility complex (MHC) initiates the sequence by organizing the assembly of an active T-cell receptor (TCR) complex responsible for transmitting information down various signaling cassettes (e.g., the IP3/Ca2+, DAG/ PKC, ras/MAPK, and the PI 3-K pathways). It is proposed that CD28 may exert its costimulatory action by facilitating the assembly of an effective scaffold of signaling elements within the TCR complex. The absence of costimulation through CD28 seems to result in the assembly of a defective scaffold that reverses slowly and may thus account for the state of unresponsiveness responsible for peripheral T-cell tolerance. The signaling cassettes activated by the TCR and CD28 then engage cytosolic factors that transmit information into the nucleus to activate the genes that code for the IL-2 and Fas signaling pathways. The IL-2 and Fas receptors employ additional signaling cassettes (e.g., the JAK/STAT and the sphingomyelinase/ceramide pathways) to mediate their effects on proliferation and apoptosis, respectively. Info...Continue Reading

Citations

Sep 11, 2019·Cold Spring Harbor Perspectives in Biology·Hwei Ling Ong, Indu Suresh Ambudkar
Mar 24, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Martin D BootmanColin W Taylor
Mar 23, 2021·Human Immunology·Nathalie Rouas-FreissEdgardo D Carosella
Aug 20, 2021·International Journal of Biological Macromolecules·Xiuge GaoDawei Guo

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