Our laboratory is dedicated to unraveling the cellular and molecular interactions that dictate the function of this lymphocyte subset in the body. This has been challenging because the helper T cells that are specific for a particular peptide:MHCII ligand are extremely rare in the total T cell population. To circumvent this problem, we developed a technique whereby a small number of monoclonal CD4+ T cells specific for a single peptide:MHCII ligand are transferred into a normal mouse. Tracking this population of T cells using flow cytometry and confocal microscopy has allowed us to visualize and identify the roles of various antigen-presenting cells, costimulatory receptors, and lymphokines during the early phases of the helper T cell response.
We recently developed a method based on peptide:MHCII tetramers and magnetic bead enrichment that has the sensitivity to detect individual peptide:MHCII-specific T cells in unmanipulated mice. This powerful technique circumvents the caveat that adoptive transfer of monoclonal T cells may not always accurately reflect the true in vivo behavior of helper T cells. We have found that the size of the initial naive repertoire for individual CD4+ antigen specific T cells varies widely from antigen to antigen and that this initial population size ultimately predicts the magnitude of the response.
Our current research is aimed at using these tools to gain insight into T cell development, activation, and memory in the mouse to set the stage for similar studies in humans. Our hope is that this basic knowledge will ultimately be used to improve vaccines and prevent unwelcome T cell responses such as autoimmunity and graft rejection.