Key Points
A naturally processed L. major peptide was identified and used to make a tetramer.
DLD-specific CD4+ T cells produce effector cytokines and display memory function.
Vaccination with rDLD protein induces strong protection against virulent challenge.
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 (DLD63–79) 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-Ab-DLD63–79 tetramer and identified DLD-specific CD4+ T cells at clonal level. Following L. major infection, DLD63–79–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.
Footnotes
This work was supported by the Canadian Institutes for Health Research (MOP 114923).
The online version of this article contains supplemental material.
- Received March 27, 2020.
- Accepted July 2, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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