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Do T cells need endogenous peptides for activation?

Nature Reviews Immunology volume 8, pages 895–900 (2008)Cite this article

Abstract

T cells are sensitive to small numbers of antigenic peptide–MHC ligands that are distributed among an excess of endogenous peptide–MHC complexes on the surface of antigen-presenting cells. Although there are accumulating data that indicate a role for these endogenous peptide–MHC complexes in T-cell receptor triggering, whether they are necessary, and the nature of their function, is controversial. In this Opinion article, I argue that endogenous peptide–MHC complexes are required for T-cell stimulation and that their mechanism of action differs between CD4+ and CD8+ T cells.

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Figure 1: Classical model of TCR and co-receptor activity.
Figure 2: Models for how endogenous peptides aid T-cell activation.

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Acknowledgements

Work from this laboratory was supported by National Institutes of Health grants R01 GM065230 and AI074074. This is manuscript number 19648 from The Scripps Research Institute.

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Authors and Affiliations

  1. Nicholas R. J. Gascoigne is at the Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 92037, USA. gascoigne@scripps.edu,

    Nicholas R. J. Gascoigne

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Glossary

Non-stimulatory peptide

Any peptide (either exogenously or endogenously derived) that, when presented by an MHC molecule, does not stimulate a T cell that expresses a particular T-cell receptor.

Endogenous peptide

A peptide that is naturally produced by a cell and is presented by MHC class I or class II molecules. Endogenous peptides were originally identified by the sequencing of purified MHC molecules. They are generally non-stimulatory because negative selection in the thymus results in apoptosis of cells that express T-cell receptors that are reactive with endogenous, stimulatory peptides.

Immunological synapse

A large junctional structure that is formed at the cell surface between a T cell and an antigen-presenting cell; it consists of molecules that are required for adhesion and signalling.

Quantum dot

An extremely small nanocrystalline semiconductor (10–50 nm) that absorbs incident photons and emits them at a longer wavelength. Because of a phenomenon called the quantum confinement effect, the colour (wavelength) of the emitted light is determined by the size of the nanocrystal.

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Gascoigne, N. Do T cells need endogenous peptides for activation?. Nat Rev Immunol 8, 895–900 (2008). https://doi.org/10.1038/nri2431

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