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Infections with Leishmania (L.) major induce protective IFN-γ-dependent Th1/Tc1 immunity in C57 BL/6 mice as well as in immunocompetent humans. Even though antigen-specific immunity provides lifelong immunity against reinfection, a vaccine against this pathogen does not yet exist. Here, we compared the results obtained from in silico predictions of murine CD8-specific L. major peptides using the algorithm SYFPEITHI with the number and predicted affinity of known proteins/peptides. Our results indicate that the majority of 'immunodominant' epitopes of L. major have not been identified so far; thus, computer-based prediction algorithms may aid the development of an effective vaccine. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the priming of Leishmania-reactive CD8+ T cells in vivo, which does not require LMP7 to contain immunoproteasomes.

In murine leishmaniasis, healing is mediated by IFN-γ-producing CD4+ and CD8+ T cells. Thus, an efficacious vaccine should induce Th1 and Tc1 cells. Dendritic cells (DCs) pulsed with exogenous proteins primarily induce strong CD4-dependent immunity; induction of CD8 responses has proven to be difficult. We evaluated the immunogenicity of fusion proteins comprising the protein transduction domain of HIV-1 TAT and the Leishmania antigen LACK (Leishmania homolog of receptors for activated C kinase), as TAT-fusion proteins facilitate major histocompatibility complex class I-dependent antigen presentation. In vitro, TAT-LACK-pulsed DCs induced stronger proliferation of Leishmania-specific CD8+ T cells compared with DCs incubated with LACK alone. Vaccination with TAT-LACK-pulsed DCs or fusion proteins plus adjuvant in vivo significantly improved disease outcome in Leishmania major-infected mice and was superior to vaccination with DCs treated with LACK alone. Vaccination with DC+TAT-LACK resulted in stronger proliferation of CD8+ T cells when compared with immunization with DC+LACK. Upon depletion of CD4+ or CD8+ T cells, TAT-LACK-mediated protection was lost. TAT-LACK-pulsed IL-12p40-deficient DCs did not promote protection in vivo. In summary, these data show that TAT-fusion proteins are superior in activating Leishmania-specific Tc1 cells when compared with antigen alone and suggest that IL-12-dependent preferential induction of antigen-specific CD8+ cells promotes significant protection against this important human pathogen. [ABSTRACT FROM AUTHOR]