Yuri Sykulev, MD, PhD
Philadelphia, PA 19107
Most Recent Peer-reviewed Publications
- Evidence that the density of self peptide-MHC ligands regulates T-cell receptor signaling
- Enteric alpha defensins in norm and pathology.
- The mechanisms of inactivation of the Tag7-Hsp70 cytotoxic complex
- Enteric alpha defensins in norm and pathology
- Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytes
Microbiology and Immunology
Thomas Jefferson University
Research and Clinical Interests
The major goal of my research program is to understand molecular mechanisms of T cell activation. I am building the program along two principal directions. The first direction is to investigate the biochemistry of T cell receptors and other immune receptors involved in antigen recognition by T cells. Having established Drosophila-based expression system to produce soluble analogs of these molecules, we systematically investigate affinity, kinetics and thermodynamics of the reactions involving these receptors. In parallel, we also study behavior of these molecules as they appear at the surface of live cells using modern visualization techniques, such as confocal microscopy and 3D microscopy. Any information derived form these experiments promises to shed light on what is now thought to be a hallmark of T cell activation, namely, formation of molecular assemblies located in distinct membrane compartments induced by productive engagement of T cell receptors with an antigen. Various recruitment patterns of the immune receptors to the membrane activating domains are thought to trigger distinct T cell responses and, thus, provide an explanation for essential flexibility in T cell responsiveness, the most intriguing feature of T cell behavior and functions.
The second direction aims to contribute to the development of new strategies of T cell vaccination. The significance of these efforts is emphasized by widely accepted believe that the induction of an effective T cell response is necessary and essential for successful host defense against viral or bacterial infection. While many new vaccination strategies are now becoming available, there are no suitable criteria to evaluate the efficacy of T cells raised in response to vaccination. Meanwhile, these criteria would help to distinguish between more or less promising vaccines during clinical trials. Speaking succinctly, it is essential to make a distinction between "good" and "bad" T cells. Quantitative analysis of molecular interactions between the immune receptors that we are studying will be useful for establishment of such criteria.
Both directions complement each other and should have both fundamental and practical implications. This research program is supported by a research grant from NIH (RO1) and W.W. Smith Charitable Trust Award.