STRUCTURE OF A T CELL RECEPTOR BOUND TO A CLASS I MHC-PEPTIDE COMPLEX. David N. Garboczi^1,5, Partho Ghosh^1,5, Ursula Utz³, William E. Biddison⁴, and Don C. Wiley^1,2, ¹Department of Molecular and Cellular Biology and ²Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA. ³Laboratoire d'Immunologie, Institut de recherches cliniques de Montreal, Montreal, Canada H2W 1R7, ⁴Molecular Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA, ⁵These authors contributed equally to the work presented

The central recognition event in the cellular immune response is between a T cell receptor (TCR) found on the surface of a T lymphocyte and an MHCpeptide complex found on the surface of a cell being inspected by the T lymphocyte. A TCR specific for HLA-A2 complexed with a peptide from the Tax protein of human T lymphotropic virus type 1 (HTLV-1) has been expressed in E. cold as inclusion bodies, refolded, and purified. This TCR binds specifically to its in vivo target, HLA-A2/Tax peptide, as seen by gelshift assays using HLA-A2 also expressed in E. cold as inclusion bodies and refolded. The ternary complex of TCR/peptide/MHC has been crystallized and X-ray diffraction data to 2.7 Å have been collected at a synchrotron. The structure has been phased from two heavy atom derivatives and from partial molecular replacement solutions. Electron density maps from these phasing methods reveal the nature of interactions between TCR and MHC/peptide, elucidating at the atomic level the mechanism of immune surveillance.