James M. Sheil , PhD

Associate Professor Emeritus

Organization:

West Virginia University School of Medicine

Department:

Microbiology, Immunology & Cell Biology

Classification:

Faculty

Member

Organization:

West Virginia University WVU Cancer Institute

Department:

WVU Cancer Institute Research Programs

Classification:

Faculty

• PhD, University of Kentucky, 1983

Manuscripts submitted or in preparation:

Frankenberry, M.A., T.D. Schell, and J.M. Sheil. 2005. A Cloned CD8+ Cytotoxic T Cell Displays both Kb- and Db-Restricted Recognition of the Horse Cytochrome c Peptide, p41-49. (in preparation).

Frankenberry, M.A., T.D. Schell, and J.M. Sheil. 2005. Dual H-2Kb- and H-2Db-Restricted Clonal CTL Recognition of a Horse Cytochrome c Peptide is Dependent on a Critical Pro-Gly Sequence. (in preparation)

Frankenberry, M.A., W. Tarry, and J.M. Sheil. 2005. Depletion of V?9+ and V?12+ CTLs in vitro abrogates the bm19 anti-C57BL/6 alloreactive response without impairing antigen-specific CTL reactivity. (in preparation)

Frankenberry, M.A., R. Schafer, W. Tarry, and J.M. Sheil. 2005. Depletion of V?9+ and V?12+ CTLs in vitro abrogates the bm19 anti-C57BL/6 alloreactive response without impairing antigen-specific CTL reactivity. (in preparation)

Sheil, J.M., M.A. Frankenberry,T.D. Schell, K.M. Brundage, and J.B. Barnett. 2005. Propanil Exposure in Mice Induces Delayed but Sustained Abrogation of Cell-mediated Immunity through Direct Interference with Cytotoxic T Lymphocyte Function. (in preparation).

Sheil, J.M., M. A. Frankenberry, K. .M. Brundage, and J.B. Barnett. 2005. Exposure of Mice to Propanil + 2,4-D Mixture enhances the Effects of Propanil Exposure Alone. (in preparation).

Other Relevant Publications:

Sun, R., S. E. Shepherd, S. S. Geier, C. T. Thompson, J. M. Sheil, and S.G. Nathenson. 1995. Evidence that the antigen receptor on cytotoxic T lymphocytes interacts with a common recognition on the H-2Kb molecule. Immunity 3: 573-582.

Schafer, R. and J. M. Sheil. 1995. Superantigens. Adv. Pediatric Infec. Dis. 10: 369-390.

Sheil, J.M., T.D. Schell, S.E. Shepherd, G.F. Klimo, J.M. Kioschos, and Y. Paterson. 1994. Presentation of a horse cytochrome c peptide by multiple H-2b class I MHC molecules to B6-and bml-derived cytotoxic T lymphocytes: Presence of a single MHC anchor residue may confer efficient peptide-specific CTL recognition. Eur. J. Immunol. 24: 2141-2149.

Yun, T.J., M.D. Tallquist, E.M. Rohren, J.M. Sheil, and L.R. Pease. 1994. Minor pocket B influences peptide binding, peptide presentation and alloantigenicity of H-2Kb. Internat. Immunol. 6 (7):1037.

Shepherd, S. E., R. Sun, S. G. Nathenson, and J. M. Sheil. 1992. Selective reactivity of CD8-independent T lymphocytes to a cytotoxic T lymphocyte-selected H-2Kb mutant altered at position 222 in the [alpha] 3 domain. Eur. J. Immunol. 22: 647-653.

Sheil, J.M., S.E. Shepherd, G.F. Klimo, and Y. Paterson. 1992. Identification of an autologous insulin B chain peptide as the target antigen of H-2Kb-restricted cytotoxic T lymphocytes. J. Exper. Med. 175(2): 545-552.

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Academic Interests

Our laboratory’s research program is focused on the response of cytotoxic T lymphocytes (CTL) to foreign antigens as critical effectors of cell-mediated immunity. The emphasis of this research focus is ultimately on understanding the role of and manipulating cytotoxic T lymphocytes in human disease states.

Current project interests include:

• A major project concerns the identification and elimination of CTLs that specifically respond to allogeneic MHC molecules on the cell surface of transplanted donor tissue or organ grafts in allograft rejection. Current clinical transplantation approaches are based on the broad-based immune suppression of a transplant patient’s T lymphocytes to prevent or delay graft rejection. We have shown in a mouse model (2 manuscripts in preparation) that two (out of 14) TCR V families control the in vitro alloreactive CTL-mediated lysis of donor cells, as a model system for transplantation rejection. By eliminating these TCR families in vivo, using a mouse skin allograft model, we find there is up to a 3-fold increase in the length of skin graft survival. We are presently developing this model for prevention of allograft rejection in humans, as well as defining the potential of this approach in other disease models, such as autoimmunity.
• Another area of interest is in the identification of autoreactive CTLs in a Type I diabetes mouse model that may be specific for the insulin B chain peptide p7-15; this peptide if shown to be an antigenic target for autoreactive CTLs could be used in a therapeutic regimen to treat or prevent the development of Type I diabetes.
• A third area of active interest concerns the immunotoxic effects of combined exposure of cytotoxic T lymphocytes to propanil and 2,4-D, two environmental chemicals that have adverse effects on the immune system. Interestingly, our studies thus far have shown a minimal effect early on following propanil+ 2,4-D exposure, but dramatic inhibition of CTL function long-term.
• A fourth area of research interest and activity concerns identifying the peptide antigen target for dominant CTLs specific for Candida albicans in a murine candidiasis model to better understand how CTLs might be activated to respond in candidiasis and other disease states induced by pathogens. This is a particularly important problem in immunosuppressed individuals, including cancer patients, transplant recipients, and others.

Alexander B. Osborn Hematopoietic Malignancy and Transplantation Program