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Ligand-specific oligomerization of T-cell receptor molecules

Nature volume 387, pages 617–620 (1997)Cite this article

Abstract

T cells initiate many immune responses through the interaction of their T-cell antigen receptors (TCR) with antigenic peptides bound to major histocompatibility complex (MHC) molecules. This interaction sends a biochemical signal into the T cell by a mechanism that is not clearly understood. We have used quasi-elastic light scattering (QELS) to show that, in the presence of MHC molecules bound to a full agonist peptide, TCR/peptide–MHC complexes oligomerize in solution to form supramolecular structures at concentrations near the dissociation constant of the binding reaction. The size of the oligomers is concentration dependent and is calculated to contain two to six ternary complexes for the concentrations tested here. This effect is specific as neither molecule forms oligomers by itself, nor were oligomers observed unless the correct peptide was bound to the MHC. These results provide direct evidence for models of T-cell signalling based on the specific assembly of multiple TCR/peptide-MHC complexes1,2,3,4 in which the degree of assembly determines the extent and qualitative nature of the transduced signal5. They may also explain how T cells maintain sensitivity to antigens present in only low abundance on the antigen-presenting cell.

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Figure 1: Distribution of scattered intensity versus Rh as obtained for 2B4, MCC–Ek and MCC–Ek.
Figure 2: Oligomerization of 2B4/MCC–Ek.
Figure 3: Complex formation is necessary for TCR/MHC oligomerization.

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Acknowledgements

All authors contributed equally to this work. We thank L. Nguyen and S. Erickson-Ybarra for help in the preparation of I-Ek and 2B4, and I. Rousso for help in sample preparation for the QELS experiments. D.S.L. is supported by a Howard Hughes Medical Institute predoctoral fellowship. J.J.B. was supported by an NIH training grant and a fellowship from the Irvington Institute for Medical Research. This work was supported by grants to M.M.D. from the NIH and the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. *Howard Hughes Medical Institute, School of Medicine, Stanford, 94305-5402, California, USA

    Ziv Reich, Daniel S. Lyons & Mark M. Davis

  2. †Department of Microbiology and Immunology, Stanford University, 94305-5402, California, USA

    J. Jay Boniface

  3. ‡The Center for Technological Education, Holon, Israel

    Nina Borochov

  4. §Chemical Serivce Unit, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Ellen J. Wachtel

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  1. Ziv Reich
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Correspondence to Mark M. Davis.

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Reich, Z., Boniface, J., Lyons, D. et al. Ligand-specific oligomerization of T-cell receptor molecules. Nature 387, 617–620 (1997). https://doi.org/10.1038/42500

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