Identification and characterization of host-protective T-cell epitopes of a major surface glycoprotein (gp63) from Leishmania major.
By using a series of overlapping synthetic peptides that cover more than 75% of the amino acid sequence of the major surface glycoprotein (gp63) from Leishmania major, 11 T-cell epitopes in CBA and BALB/c mice have been identified. Six of the peptides were recognized by T cells of CBA mice recovered from L. major infection, while one was recognized by the T cells from BALB/c mice recovered from the infection following sublethal doses of gamma-irradiation. Lymph node cells from mice immunized with the peptides also responded to a number of the same peptides (seven in CBA and one in BALB/c). Peptide p10-28 induced proliferative T-cell responses in both CBA and BALB/c mice. Five of the peptides (p10-28, p22-40, p289-309, p459-471 and p467-482) induced vigorous T-cell response in CBA mice but were not recognized by T cells from recovered mice. Four other peptides (p321-336, p364-476, p372-385 and p378-396) were recognized by T cells from recovered CBA mice but could not induce a T-cell response in normal CBA mice. Three peptides (p146-171, p289-309 and p395-414) were both able to induce a T-cell response and were recognized by T cells from recovered mice. However, only two peptides (p146-171 and p467-482) were able to activate T cells, which also recognized epitopes expressed by antigen-presenting cells infected with promastigotes. T cells induced by p146-171 and p467-171 or a mixture of these two peptides were mainly CD4+ and produced interleukin (IL-2) and interferon-gamma (IFN-gamma) but not IL-4 upon antigen stimulation in vitro. These two peptides also induced a classical delayed type hypersensitivity (DTH) response in CBA mice. Furthermore, CBA mice immunized with a mixture of the two peptides in Coryne parvum or entrapped in liposomes induced significant resistance against L. major infection. The implications of these results in terms of a synthetic vaccine against leishmaniasis and the mechanism of the induction of Th1 and Th2 cells are discussed.
Yang
D M
DM
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, Kent, U.K.
Rogers
M V
MV
Liew
F Y
FY
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry*; D006790:Host-Parasite Interactions; D006968:Hypersensitivity, Delayed / Q000469:parasitology; D007110:Immunity, Active; D007895:Leishmania tropica / Q000276:immunology*; D007896:Leishmaniasis / Q000517:prevention & control; D008222:Lymphokines / Q000737:chemistry; D008666:Metalloendopeptidases; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010641:Phenotype; D015800:Protozoan Proteins / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000302:isolation & purification
D000953:Antigens, Protozoan; D008222:Lymphokines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania