In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323-339). Immunization with M-OVA323-339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4+ T cells revealed that immunization with M-OVA323-339 induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo. However, these T cells developed only poor effector functions, reflected by minimal IFN-γ production, low IgG2a levels in serum and poor peptide-specific delayed-type hypersensitivity (DTH) responses. This diminished inflammatory response was associated with decreased infiltration of T cell blasts and macrophages. Importantly, also mice with functional effector T cells did not mount a robust DTH response after a challenge with M-OVA323-339 in the ear, although their T cells responded normally to M-OVA323-339 in vitro. In conclusion, mannosylated peptide induces proliferation of T cells with impaired Th1 cell effector functions and additionally abrogates the activity of pre-existing effector T cells. © The Japanese Society for Immunology. 2007. All rights reserved.