Molecular cloning of a novel protein antigen of Leishmania major that elicits a potent immune response in experimental murine leishmaniasis
Webb, J.R.; Kaufmann, D.; Campos-Neto, A.; Reed, S.G.
Journal of Immunology 157(11): 5034-5041
1996
ISSN/ISBN: 0022-1767 PMID: 8943412 Document Number: 459683
Sera from Leishmania major (Friedlan strain)-infected BALB/c mice were used to screen an L. major amastigote cDNA expression library. One of the 4 clones detected encodes a novel antigen designated as L. major stress-inducible 1 (LmSTI1). The gene was sequenced and expressed. LmSTI1 contains 6 copies of the tetratricopeptide consensus motif and is highly related to a family of stress-inducible proteins that is conserved from yeast to humans; it was found in both promastigotes and amastigotes. Sera from L. major-infected BALB/c mice have LmSTI1-specific antibody titres in excess of 1:200 000, comprised predominantly of IgG1, IgG2A, and IgG2B isotypes. Recombinant LmSTI1 protein elicited strong proliferative responses from draining lymph node cells of L. major-infected BALB/c mice at both early (10 days) and late (28 days) stages of infection and elicited production of high levels of interferon (IFN)- gamma and low levels of interleukin (IL)-4 (Th1 response), in contrast to soluble leishmanial lysate, which elicited high levels of IL-4 and low IFN- gamma production (Th2 response). In addition, analyses of sera from human patients with cutaneous (L. major), visceral, and post-kala azar dermal (L. donovani) leishmaniasis indicated that a majority of individuals from all 3 clinical groups mounted strong humoral responses against LmSTI1, suggesting that the serologic determinants of LmSTI1 are conserved between the 2 Leishmania species. The nucleotide sequence of the gene has been submitted to GenBank under the accession number U73845.