The research of Peter J. Wettstein, Ph.D., focuses on the characterization of non-H-2 histocompatibility genes and the regulation of T lymphocyte responses to these genes' antigenic products in mice. Dr. Wettstein also investigates environmental effects on immunoregulatory gene family evolution and selection. Additionally, he is interested in monitoring both innate and adaptive immune responses in human patients and large-animal models of organ and tissue transplantation.
Mechanisms of histocompatibility antigen immunodominance. Dr. Wettstein is working to refine the hierarchy of immunodominant antigens, to define the role of H-2-linked genes in selecting immunodominant antigens, and to evaluate the interaction of helper and cytolytic T cells specific to different classes of immunodominant antigens.
He also investigates the role of H-2-linked genes in defining the magnitude and specificity of the T cell response to histocompatibility antigens. These latter studies involve investigation into the diversity and characteristics of receptors on histocompatibility antigen-specific T cells and their relationships to the characteristics of the antigens that they are specific for.
- Differential regulation by both H-2-linked genes and T cell subpopulations. Dr. Wettstein studies regulation of cytolytic and helper T cell generation in vitro, and compares this process with regulation in skin graft rejection, graft-versus-host disease and responses to viral infections.
- Environmental factors regulating immune response. Dr. Wettstein carries out direct investigation of the role of environmental factors on the evolution and maintenance of diversity in gene families that regulate the mammalian immune response. He also works to estimate the time of subspeciation and the extent of divergence of both immunoregulatory gene families and genes that experience less selective pressure.
- Immune monitoring. Dr. Wettstein is focused on the development and adaptation of methods for monitoring innate and adaptive immune responses and on the development of clinical protocols, large-animal models and grant submissions. Monitoring efforts include evaluation of the diversity of T and B cell repertoires in human cancer patients, cytokine expression following human and nonhuman lymphocyte activation, and T cell responses to histocompatibility antigens following cell and organ transplantation in large-animal models.
Significance to patient care
Dr. Wettstein's research provides new data that will be important for developing new vaccines and understanding the effects of aging. His work on T cell monitoring of patients in immunotherapy trials is aimed at improving the efficacy and safety of cancer therapies, thereby contributing to better overall outcomes for patients with cancer. His study of immune responses in large-animal transplant recipients will be important for translation to human transplantation.