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*
Corixa Corporation, Seattle, WA 98104;
College of Medicine, King Khalid University, Abha, Saudi Arabia;
Infectious Disease Research Institute, Seattle, WA 98104;
Federal University of Bahia, Salvador, Bahia, Brazil; and
¶ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada
Persistent immunity against Leishmania infections in
humans is mediated predominantly by CD4+ T cells of the Th1
phenotype. Herein we report the expression cloning of eight
Leishmania Ags using parasite-specific T cell lines
derived from an immune donor. The Ags identified by this technique
include the flagellar proteins 
- and 
-tubulin, histone H2b,
ribosomal protein S4, malate dehydrogenase, and elongation factor 2, as
well as two novel parasite proteins. None of these proteins have been
previously reported as T cell-stimulating Ags from
Leishmania. -tubulin-specific T cell clones generated
against Leishmania major amastigotes responded to
Leishmania-infected macrophages and dendritic cells.
IFN-
enzyme-linked immunospot analysis demonstrated the presence of
T cells specific for several of these Ags in PBMC from self-healing
cutaneous leishmaniasis patients infected with either Leishmania
tropica or L. major. The responses elicited by
Leishmania histone H2b were particularly striking in
terms of frequency of histone-specific T cells in PBMC (1 T cell
of 6000 PBMC) as well as the percentage of responding donors (86%, 6
of 7). Ags identified by T cells from immune donors might constitute
potential vaccine candidates for leishmaniasis.
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