Paul Hess, DVM, PhD
Associate Professor, Oncology & Immunology
- BA, English, Biology; Rutgers University, 1985
- DVM; Mississippi State University, 1992
- PhD, Immunology; North Carolina State University, 2002
- Residency, Small Animal Internal Medicine; NCSU,1994-1997
- Post-doctoral Research, Frelinger Lab, Department of Microbiology & Immunology, University of North Carolina at Chapel Hill School of Medicine, 2003-2008
- Residency, Medical Oncology; NCSU, 2002-2008
- Diplomate, ACVIM, Small Animal Internal Medicine, Oncology
- Graduate Faculty, NCSU Immunology Program
- Member, NCSU Biotechnology Program
- Member, NCSU Center for Comparative Medicine and Translational Research
- Visiting Scientist, Department of Microbiology & Immunology, UNC-CH SOM
CD8+ T cells are important effectors of the adaptive immune response, functioning mainly to remove infected cells from the body, which they detect by recognizing short peptides derived from microbial proteins that are displayed within the binding groove of class I major histocompatibility complex (MHC) molecules on the cell surface. When the T cell receptor binds to its specific peptide-MHC partner, the T cell is triggered, killing the infected cell. In a healthy animal, there are numerous regulatory safeguards in place to prevent inadvertent triggering by “self” peptide-MHC (pMHC) complexes. In some immune-mediated conditions, such as type 1 diabetes, this normal tolerance is disabled, and self-reactive T cells are inappropriately activated, causing destruction of healthy tissue, and eventually, clinical signs of the disease. Similarly, in allotransplantation, normal CD8+ T cell responses of the recipient that are directed against donor antigens can lead to graft rejection. Unfortunately, in either condition, long-term inhibition of T cell responses with non-specific immunosuppressive drugs carries risks of cancer and serious infections.
Selective deletion of the pathogenic CD8+ T cells would appear to be an optimal strategy, but until recently, there has been no efficient means of targeting just the culprits, which constitute a very tiny fraction of the overall T cell pool. Altman et al. demonstrated that CD8+ T cells of known specificity could be differentiated from other T cells in mixed populations by the use of soluble complexes, widely known as “tetramers”, consisting of four identical pMHC molecules bound to streptavidin. When coupled to fluorescent molecules, tetramers allow ready visualization of epitope-specific T cells by flow cytometry, the most common use of this technology. In our laboratory we have shown that such tetramers can be used to deliver a potent cytotoxin to specific T cells (see the figure below), eliminating the targeted cells, while leaving protective T cells unharmed. This strategy represents a new and potentially useful immunotherapy approach for T cell-mediated autoimmune diseases and complications of allotransplantation, and is a major focus of the lab.
A second focus is the discovery of new peptide epitopes in viral diseases and allograft rejection. Lastly, our laboratory also investigates novel clinical predictors of chemotherapy resistance and toxicity in dogs with lymphoma.
Left to right: Sabrina Murray, Graduate Student, Immunology; Peter Borgheiinck, Graduate Student,
Immunology; Paul Hess, PI; Savannah Gabriel, Research Technician; Greg Gojanovich, Graduate
Left to right: Jason Kidd, Resident, Medical Oncology; Lesia Denysyk DVM Student
Vincent BG, Young EF, Buntzman AS, Stevens R, Kepler TB, Tisch RM, Frelinger JA, and Hess PR. Toxin-Coupled MHC Class I Tetramers Can Specifically Ablate Autoreactive CD8+ T Cells and Delay Diabetes in Nonobese Diabetic Mice. Journal of Immunology 2010; Epub ahead of print.
Young EF, Hess PR, Arnold LW, Tisch RM and Frelinger JA. Islet lymphocyte subsets in male and female diabetes-prone NOD mice are qualitatively similar but quantitatively distinct. Autoimmunity 2009; 42(8): 678-91.
Hess PR, Barnes C, Woolard MD, Johnson MD, Cullen JM, Collins EJ, and Frelinger JA.. Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 2007; 109(8):3300-3307.
Young EF, Talmage G, Larry FW, Buntzman A, Hess P, Tisch R, Frelinger J. Naïve T cells found in the islets of NOD mice do not cause type 1 diabetes. American Association of Immunologists (AAI) Annual Meeting, 2010.
Murray SL, Miller KR, Young EF, Vincent BG, Steele SP, Buntzman AS, Collins EJ, Frelinger JA, Hess PR. Cytotoxic class I tetramers inhibit CTL priming and alter immunodominance hierarchies in the HY model system. AAI Annual Meeting, 2010.
Cora MC, Neel JA, Grindem CB, Hess PR. Comparison of automated WBC and manual WBC differential for the detection of cytopenias and cellular abnormalities in dogs receiving chemotherapy. American College of Veterinary Pathologists (ACVP) Annual Meeting, 2009.
Kidd JA, Buntzman AS, Borgheiinck PR, Hess PR. Circulating antibodies to L-asparaginase are detectable via ELISA in dogs treated with lymphoma. Veterinary Cancer Society (VCS) Annual Meeting, 2009.
Young EF, Vincent B, Buntzman A, Tisch R, Frelinger JA, Hess PR. Long term elimination of epitope specific diabetogenic CD8+ T cells using toxin coupled tetramers in NOD mice. AAI Annual Meeting, 2009.
Hess PR, Murray SL, Buntzman AS, Young EF, Steele SP, Collins EJ, Frelinger JA. Selective deletion of HY-reactive CD8+ T cells by saporin-coupled MHC class I tetramers. AAI Annual Meeting, 2009.
Links of Interests