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The nature of molecular recognition by T cells

Nature Immunology volume 4, pages 217–224 (2003)Cite this article

Abstract

Considerable progress has been made in characterizing four key sets of interactions controlling antigen responsiveness in T cells, involving the following: the T cell antigen receptor, its coreceptors CD4 and CD8, the costimulatory receptors CD28 and CTLA-4, and the accessory molecule CD2. Complementary work has defined the general biophysical properties of interactions between cell surface molecules. Among the major conclusions are that these interactions are structurally heterogeneous, often reflecting clear-cut functional constraints, and that, although they all interact relatively weakly, hierarchical differences in the stabilities of the signaling complexes formed by these molecules may influence the sequence of steps leading to T cell activation. Here we review these developments and highlight the major challenges remaining as the field moves toward formulating quantitative models of T cell recognition.

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Figure 1: The wide variation in the 2D and 3D affinities of leukocyte cell-cell recognition molecules.
Figure 2: Structural rearrangements accompany TCR-peptide-MHC interactions.
Figure 3: Coreceptor interactions and structure: implications of hierarchical affinity differences.
Figure 4: Contrasting modes of low-affinity recognition at the leukocyte surface.
Figure 5: Diverse stabilities and organization of signaling structures formed by costimulatory molecules.
Figure 6: Electrostatic contacts determine the specificity of CD2 binding to CD58.

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Acknowledgements

We thank E.Y. Jones, D.I. Stuart, A.N. Barclay and P. Sørensen for valuable discussion, and J.T. Finch for permission to use the electron micrographs of rat CD4 ectodomains. S.J.D. and P.A.v.d.M. are supported by the Wellcome Trust and the UK Medical Research Council, respectively. S.I. is supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. L.F. is supported by the Karen Elise Jensen Foundation, The Danish MS Society and the UK Medical Research Council.

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Authors and Affiliations

  1. Nuffield Department of Clinical Medicine, Weatherall Institute of Molecular Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

    Simon J. Davis & Edward J. Evans

  2. MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

    Lars Fugger

  3. Division of Structural Biology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, 862-0973, Japan

    Shinji Ikemizu

  4. Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Talitha R. Bakker & P. Anton van der Merwe

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Correspondence to Simon J. Davis or P. Anton van der Merwe.

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Davis, S., Ikemizu, S., Evans, E. et al. The nature of molecular recognition by T cells. Nat Immunol 4, 217–224 (2003). https://doi.org/10.1038/ni0303-217

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