Structural Analysis of the Human T-Cell Receptor/HLA-A2/Peptide Complex.

During the first year of the grant, we obtained sufficient amounts of the T-cell receptor TCR for crystallization experiments. This was achieved by protein engineering and by protein refolding experiments. The refolded TCR is now readily obtained in large amounts. The refolded TCR binds to its specific peptideHLA-A2 complex as detected by native polyacrylamide gel electrophoresis. The ternary complex of TCRHLA-A2peptide forms large moderately-well diffracting crystals. We have collected a 3.3 Angstrom dataset and are in the process of determining the structure of the complex to the limit of our data. This structural determination of the T-cell receptorHLA-A2peptide complex should allow a detailed understanding of this central molecular recognition event in the immune system.