Lymphocyte Activation: Signal Transduction

Abstract

Adaptive immunity depends on the transfer of information across the plasma membrane of T and B lymphocytes. This information takes the form of signal transduction pathways that are initiated by the recognition of antigens by specific transmembrane receptors, and that result in a complex series of biochemical changes within the cell that ultimately alter cellular function. A key feature of antigen receptors on T and B lymphocytes is that they contain no intrinsic catalytic activity. Rather, they signal through the initial activation of nonreceptor tyrosine kinases, which then phosphorylate various cytoplasmic and membrane‐bound adaptor proteins. These adaptor proteins function as molecular scaffolds for the further activation of downstream signalling pathways that mediate the ultimate effects of antigen recognition on lymphocyte function, including modification of transcription factors and changes in the cytoskeleton.

Key Concepts:

  • Lymphocyte antigen receptors consist of separate modules for antigen recognition and signal transduction.

  • Lymphocyte antigen receptors contain no intrinsic catalytic activity, but rather link to nonreceptor tyrosine kinases.

  • The immunoreceptor tyrosine‐based activation motif is critical for linking antigen receptors to tyrosine kinases.

  • Both cytoplasmic and transmembrane adaptor proteins are important for translating proximal antigen receptor signalling to common downstream signalling pathways.

  • Downstream effectors of antigen receptor signalling include serine/threonine kinases and small G proteins.

  • Antigen‐receptor signalling can be modulated by other coreceptors expressed by lymphocytes.

  • Antigen‐receptor signalling is critical for both activation of mature lymphocytes as well as for their development in the bone marrow or thymus.

Keywords: signal transduction; lymphocytes; receptors; phosphorylation; immunity

Figure 1.

The signalling pathways following BCR stimulation. Molecules in red are major signalling components that are phosphorylated after BCR crosslinking. Arrows represent either phosphorylation induced after BCR ligation or connection between signalling molecules and downstream events or components. Coreceptors that play regulatory roles in BCR signalling are shown in colour.

Figure 2.

The signalling cascades activated by the TCR. The major signalling molecules that become tyrosine phosphorylated following TCR‐CD4/CD8 crosslinking are shown in red.

Figure 3.

Putative phosphatidylinositol pathway and calcium flux induced by crosslinking of the BCR or TCR.

close

References

Coward J, Germain RN and Altan‐Bonnet G (2010) Perspectives for computer modeling in the study of T cell activation. Cold Spring Harbor Perspectives in Biology 2(6): a005538.

Deane JA and Fruman DA (2004) Phosphoinositide 3‐kinase: diverse roles in immune cell activation. Annual Review of Immunology 22: 563–598.

Gold MR, Law DA and DeFranco AL (1990) Stimulation of protein tyrosine phosphorylation by the B‐lymphocyte antigen receptor. Nature 345: 810–813.

Grakoui A, Bromley SK, Sumen C et al. (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285: 221–227.

Macian F (2005) NFAT proteins: key regulators of T‐cell development and function. Nature Review Immunology 5: 472–484.

van der Merwe PA and Dushek O (2011) Mechanisms for T cell receptor triggering. Nature Reviews Immunology 11: 47–55.

Schulze‐Luehrmann J and Ghosh S (2006) Antigen‐receptor signaling to nuclear factor kappaB. Immunity 25: 701–715.

Weiss A and Littman DR (1994) Signal transduction by lymphocyte antigen receptors. Cell 76: 263–274.

Wherry EJ (2011) T cell exhaustion. Nature Immunology 12: 492–499.

Further Reading

Bolen JB (1995) Protein tyrosine kinases in the initiation of antigen receptor signaling. Current Opinion in Immunology 7: 306–311.

Chan C, Desai DM and Weiss A (1994) The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction. Annual Review of Immunology 12: 555–592.

Chi H (2012) Regulation and function of mTOR signalling in T cell fate decisions. Nature Reviews Immunology 12: 325–338.

Dal Porto JM, Gauld SB, Merrell KT et al. (2004) B cell antigen receptor signaling 101. Molecular Immunology 41: 599–613.

Gascoigne NRJ and Palmer E (2011) Signaling in thymic selection. Current Opinion in Immunology 23: 207–212.

Mustelin T, Vang T and Bottini N (2005) Protein tyrosine phosphatases and the immune response. Nature Review Immunology 5: 43–57.

Odorizzi PM and Wherry EJ (2012) Inhibitory receptors on lymphocytes: insights from infections. Journal of Immunology 188: 2957–2965.

Samelson LE (2002) Signal transduction mediated by the T cell antigen receptor: the role of adapter proteins. Annual Review of Immunology 20: 371–394.

Waickman AT and Powell JD (2012) Mammalian target of rapamycin integrates diverse inputs to guide the outcome of antigen recognition in T cells. Journal of Immunology 188: 4721–4729.

Wang L, Xiong Y and Bosselut R (2010) Tenuous paths in unexplored territory: from T cell receptor signalling to effector gene expression during thymocyte selection. Seminars in Immunology 22: 294–302.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
P Kane, Lawrence(May 2013) Lymphocyte Activation: Signal Transduction. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001185.pub3]