Structural characterization of the TCR complex by electron microscopy

Arechaga, Ignacio
Swamy, Mahima
Abia, David
Schamel, Wolfgang A.
Alarcón, Balbino
Valpuesta, José María

¹Departamento de Biología Molecular, Universidad de Cantabria (UC) and Instituto de Biomedicina y Biotecnología de Cantabria, IBBTEC (CSIC-UC-IDICAN), c/Herrera Oria s/n, 39011 Santander, Spain
²Max-Planck-Institute of Immunobiology and Centre for Biological Signalling Studies (bioss), Faculty of Biology, and Centre for Chronic Immunodeficiency, CCI, Department of Molecular Immunology, University of Freiburg, 79108 Freiburg, Germany
³Centro de Biología Molecular Severo Ochoa
⁴Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain

Correspondence to: W. Schamel; E-mail: [email protected]

Received May 05, 2010

Accepted August 20, 2010

International Immunology 22(11):p 897-903, November 2010. | DOI: 10.1093/intimm/dxq443

Structural information on how the TCR transmits signals upon binding of its antigen peptide MHC molecule ligand is still lacking. The ectodomains of the TCRα/β, CD3εγ and CD3εδ dimers, as well as the transmembrane domain of CD3ζ, have been characterized by X-ray crystallography and nuclear magnetic resonance (NMR). However, no structural data have been obtained for the entire TCR complex. In this study, we have purified the TCR from T cells under native conditions and used electron microscopy to derive a three-dimensional structure. The TCR complex appears as a pear-shaped structure of 180 × 120 × 65

. Furthermore, the use of mAbs has allowed to determine the orientation of the TCRα/β and CD3 subunits and to suggest a model of interactions. Interestingly, the reconstructed TCR is larger than expected for a complex with a αβγεδεζζ stoichiometry. The accommodation of a second TCRαβ to fill in the extra volume is discussed.