Structural investigation of T cell immunology and cell adehesion The central issue of T cell immunity is that a T cell receptor recognizes a cognate antigenic peptide presented by a MHC molecule on antigen-presenting surface. The interaction is aided by co-receptors CD4 and CD8 in helper T cell (class II) and cytotoxic T cell (class I), respectively. We have been working out structures of T cell receptor (TCR) and its complex with antigenic peptides bound to MHC molecule in both class I and II systems. We have also been worked out the structures of co-receptors CD8 and CD4 in complex with classic or non-classic MHC molecules. We have provided the structural basis for cellular immune recognition. In the future, we will explore the developmental aspect of cellular immunity and mechanism of autoimmunity from structural point of view.
Another important research line has to do with the structural basis of cell adhesion. Cell adhesion is extremely important in immune surveillance and the formation of immunological synapse, the key local contacts between immune cells and antigen-presenting cells. For example, we have been studying how ICAM family members interact with integrin LFA-1 at atomic resolution detail and CD2 interacts with CD58 from opposing cell surfaces. Cell adhesion is also vital for tissue maintenance and nervous system development. We have determined structure of N-terminal two-domain of E-cadherin, the molecule that plays a key role for epithelial tissue formation. More recently, we have solved the structure of a headpiece of a fascinating receptor molecule Dscam from Drosophila. Dscam has unprecedented 38,000 isoforms generated by alternative splicing from a single gene. The molecule serves both for neuronal wiring process and immune response. We have identified two epitopes on the structure, which may explain how this molecule works in homophilic adhesion to determine the network wiring process of a neural system, and possible heterophilic interaction with pathogen.
From these works we have formulated some principal of protein-protein interactions from opposing cell surfaces. We have summarized the unique structural features of this interaction as opposed to protein-protein interaction in solution.