Peptide immunization excludes antigen-specific T cells from splenic lymphoid compartments.

Using adoptive transfer of TCR-transgenic T cells, we examined the homing of transgenic T cells to splenic compartments in situ. After systemic immunization with peptide or protein antigen, the location of clonotypic T cells, cytokine production, cell surface markers, and apoptosis were assessed. There were distinct differences in the splenic homing of CD4(+) TCR-transgenic T cells in mice immunized with peptide as compared to mice immunized with whole-protein antigen. T cells in peptide-immunized mice were found almost exclusively in the splenic red pulp, but not in the T and B cell zones (white pulp), while the majority of T cells immunized with whole protein were found in the white pulp. Many more Fas ligand-expressing and apoptotic cells were present after peptide immunization than after whole-protein immunization. Localization of IL-4-, IL-2- and IFN-gamma-producing cells to the lymphocyte-containing splenic white pulp was only observed with whole-protein immunization. The unique homing and increased apoptosis of immune cells post peptide immunization may help explain the ineffectiveness of many peptide vaccines. Linkage of the same peptide epitope to a carrier protein increased white pulp T cell localization and decreased apoptosis, suggesting a strategy to enhance peptide vaccine responses.