SPECIFICITY AND MODULATION OF VIRUS INDUCED MEMORY CELLS

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I am a physician with a strong commitment not only to patient care but also to medical research , which is well demonstrated by my carer history. I obtained m MD at Dalhousie University, Halifax, N.S.. During this time I was already actively involved as a medical student in endocrine research resulting in 3 publications. I went on to obtain my internal medicine training at the same institution., followed by subspecialty training in infectious diseases at the leading Canadian center at the University of Manitoba, Winnipeg, Mb.. With Medical Research Council of Canada funding I pursued my interest in human immune defenses and obtained a PhD, in the medical Microbiology Department at the University of Manitoba. My thesis work focused on human NK and gammadelta T cell responses to tumors. I felt that further training with immunological responses to viruses would complement both my clinical and research interests. I therefore joined Dr. Raymond Welsh's Lab, Pathology Dept., University of Massachusetts Medical Center, 3 years ago for postdoctoral training. Working with Dr. Welsh, has led to my making some novel observations which pertain not only to viral immunology but to basic immuno theory. I have shown that acute viral infections, generate cytotoxic T lymphocytes (CTL) cross-reactive with heterologous viruses in mice. A heterologous viral infection can prime a CTL response and provide some protective immunity to a second viral infection, and subsequent to the second viral infection, the memory CTL response to the first virus becomes partially deleted. I envision an immunological network of memory cells that, by virtue of sometimes remote cross-reactivities, are continually being modulated by infectious agents and environmental antigens. I propose here to use several viruses and synthetic viral peptides to explore the specificities of virus-induced polyclonal CTL activation and to determine the significance of crossreactive CTL in "natural" resistance to infection and virus-induced immunopathology. Specific Aims: #1 will define the kinetics of the viral peptide specificities of the CTL response to LCMV; #2 analyzes CTL responses crossreactive between different viruses; #3 tests model systems for the significance of the crossreactive responses. This is an ideal environment to achieve my ultimate goal of clinical investigator. Within Dr. Welsh's Lab I can continue to develop a strong basic science background in the field of viral immunology, at a school that has a strong interdepartmental program in viral immunology. As my work progresses I have the potential to form collaborative efforts with both Dr. Harriet Robinson, applying my models to her HIV system in macaques, and with Dr. Frank Ennis, looking at immune modulation in human infections with viruses such as influenza, HIV and EBV.