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Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor

Nature Structural Biology volume 6, pages 574–581 (1999)Cite this article

Abstract

Using NMR spectroscopy, we determined the solution structure of a single-chain T-cell receptor (scTCR) derived from the major histocompatibility complex (MHC) class II-restricted D10 TCR. The conformations of complementarity-determining regions (CDRs) 3β and 1α and surface properties of 2α are different from those of related class I-restricted TCRs. We infer a conserved orientation for TCR Vα domains in complexes with both class I and II MHC–peptide ligands, which implies that small structural variations in Vα confer MHC class preference. High mobility of CDR3 residues relative to other CDR or framework residues (picosecond time scale) provides insight into immune recognition and selection mechanisms.

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Figure 1: Sequence alignment28 of the CDRs of MHC class II-specific D10 TCR with MHC class I- specific TCRs 2C (ref. 16), A6 (ref. 9), N15 (ref. 17), KB5-C20 (ref. 18), B7 (ref. 11). KB5 = KB5-C20.
Figure 2: Ensemble of 22 backbone structures of the D10 TCR Vα and Vβ domains (in stereo).
Figure 3: Strips from an 15N-edited NOESY-HSQC spectrum (τm = 200 ms) on a uniformly 15N-labeled, 50% deuterated D10 scTCR sample.
Figure 4: TCR interaction with pMHC.
Figure 5: Backbone mobility of the D10 scTCR.

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Acknowledgements

This work was supported by the Cancer Research Institute (fellowship to B.J.H.) and the National Institutes of Health (G.W. and E.L.R.). P.S.K. acknowledges support from the Schweizerischer Nationalfond and Schweizerische Krebsliga. We thank D. Austen and K. Huestis for technical assistance. We thank S. Khandekar and B. Bettencourt for helpful discussions. We thank F. Del Rio-Portilla for assistance with coupling constant measurements.

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Author notes

  1. Daniel F. Wyss

    Present address: Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey, 07033, USA

  2. Marcia S. Osburne

    Present address: ARIAD Pharmaceuticals, Inc., 26 Landsdowne Street, Cambridge, Massachusetts, 02139

  3. Petra S. Kern

    Present address: N.V.Proctor@Gamble Eurocor S.A., Temselaan 100, A128, B-1853, Strombeek-Bever, Belgium

Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Brian J. Hare & Gerhard Wagner

  2. Procept Inc., 840 Memorial Drive, Cambridge, 02139, Massachussetts, USA

    Daniel F. Wyss & Marcia S. Osburne

  3. Department of Medicine, Harvard Medical School, and Laboratory of Immunobiology, Dana Farber Cancer Institute, Boston, 02115, Massachusetts, USA

    Petra S. Kern & Ellis L. Reinherz

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Correspondence to Gerhard Wagner.

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Hare, B., Wyss, D., Osburne, M. et al. Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor. Nat Struct Mol Biol 6, 574–581 (1999). https://doi.org/10.1038/9359

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