The rational design of synthetic vaccines would be greatly facilitated by the ability to modulate the specificity, avidity or phenotype of the elicited helper T cells. This proposal examines whether the immunization regimen can influence the antigen-specific helper T cells that are expanded during the course of an immune response. The antigen-specific stimulation of naive murine helper T lymphocytes in vivo will be studied, as well as the subsequent expansion and fate of selected T cell population. Using the well defined cytochrome c antigen system, a quantitative assay system will be developed to measure the immunogenicity of peptide antigens in vivo. Priming with antigen-pulsed syngeneic splenocytes, in the absence of adjuvant, will permit the quantitative evaluation of variables potentially important in the immunization regimen. The role of defined antigenic properties (e.g., size, conformation, affinity for the Ia molecule and the T cell receptor) will be directly tested in vivo. An attempt will be made to correlate the known antigenicity of defined peptides in vitro with their immunogenicity in vivo. The demonstration of such a correlation would strengthen the ability to apply data obtained in vitro to clinical situations, most notably vaccine development. Next, the effect of different immunization regimens on peripheral T cells will be examined. The precursor frequency, antigen-specificity and antigen-sensitivity of the elicited T cells will be followed as a function of the dose of immunogen, the nature of the immunogen, and the presence of adjuvants. Finally, defined immunization and secondary proliferative T cells response and/or affinity maturation in the T cell compartment.
