Identification of a Protective Leishmania Antigen Dihydrolipoyl Dehydrogenase and Its Responding CD4⁺ T Cells at Clonal Level

Abstract

There is currently no clinically effective vaccine against cutaneous leishmaniasis because of poor understanding of the Ags that elicit protective CD4⁺ T cell immunity. In this study, we identified a naturally processed peptide (DLD_63–79) that is derived from Leishmania dihydrolipoyl dehydrogenase (DLD) protein. DLD is conserved in all pathogenic Leishmania species, is expressed by both the promastigote and amastigote stages of the parasite, and elicits strong CD4⁺ T cell responses in mice infected with L. major. We generated I-A^b-DLD_63–79 tetramer and identified DLD-specific CD4⁺ T cells at clonal level. Following L. major infection, DLD_63–79–specific CD4⁺ T cells massively expanded and produced effector cytokines (IFN-γ and TNF). This was followed by a gradual contraction, stable maintenance following lesion resolution, and display of memory (recall) response following secondary challenge. Vaccination with rDLD protein induced strong protection in mice against virulent L. major challenge. Identification of Ags that elicit protective immunity and their responding Ag-specific T cells are critical steps necessary for developing effective vaccines and vaccination strategies against infectious agents, including protozoan parasites.