Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1993 Apr;78(4):582–585.

Immunological analysis of the zinc-binding peptides of surface metalloproteinase (gp63) of Leishmania major.

D Yang 1, M V Rogers 1, S J Brett 1, F Y Liew 1
PMCID: PMC1421896  PMID: 8495977

Abstract

The surface metalloproteinase, gp63, is highly conserved and immunogenic. A peptide spanning the zinc-binding region of the molecule is immunogenic and can induce protective immunity in mice against Leishmania major infection. We report here that the minimum length of the immunogenic peptide in this region is a heptapeptide, VVTHEMA, corresponding to residues 161-167. Optimal immunogenicity is conferred by a decapeptide, LVTVVTHEMA, corresponding to residues 158 to 167, where H and E are consensus zinc-binding residues. These two residues determine the specificity of the peptide. The next two residues, M and A are necessary for the immunogenicity of the peptide. These results suggest that the zinc-binding residues are recognized by the T-cell receptor complex, while the two adjacent residues are involved in the peptide presentation by the major histocompatibility complex (MHC) molecule.

Full text

PDF
582

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bordier C. The promastigote surface protease of Leishmania. Parasitol Today. 1987 May;3(5):151–153. doi: 10.1016/0169-4758(87)90199-2. [DOI] [PubMed] [Google Scholar]
  2. Bouvier J., Bordier C., Vogel H., Reichelt R., Etges R. Characterization of the promastigote surface protease of Leishmania as a membrane-bound zinc endopeptidase. Mol Biochem Parasitol. 1989 Dec;37(2):235–245. doi: 10.1016/0166-6851(89)90155-2. [DOI] [PubMed] [Google Scholar]
  3. Champsi J., McMahon-Pratt D. Membrane glycoprotein M-2 protects against Leishmania amazonensis infection. Infect Immun. 1988 Dec;56(12):3272–3279. doi: 10.1128/iai.56.12.3272-3279.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang K. P., Chaudhuri G., Fong D. Molecular determinants of Leishmania virulence. Annu Rev Microbiol. 1990;44:499–529. doi: 10.1146/annurev.mi.44.100190.002435. [DOI] [PubMed] [Google Scholar]
  5. Chaudhuri G., Chaudhuri M., Pan A., Chang K. P. Surface acid proteinase (gp63) of Leishmania mexicana. A metalloenzyme capable of protecting liposome-encapsulated proteins from phagolysosomal degradation by macrophages. J Biol Chem. 1989 May 5;264(13):7483–7489. [PubMed] [Google Scholar]
  6. Handman E., Mitchell G. F. Immunization with Leishmania receptor for macrophages protects mice against cutaneous leishmaniasis. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5910–5914. doi: 10.1073/pnas.82.17.5910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Howard J. G., Hale C., Liew F. Y. Immunological regulation of experimental cutaneous leishmaniasis. IV. Prophylactic effect of sublethal irradiation as a result of abrogation of suppressor T cell generation in mice genetically susceptible to Leishmania tropica. J Exp Med. 1981 Mar 1;153(3):557–568. doi: 10.1084/jem.153.3.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jardim A., Alexander J., Teh H. S., Ou D., Olafson R. W. Immunoprotective Leishmania major synthetic T cell epitopes. J Exp Med. 1990 Aug 1;172(2):645–648. doi: 10.1084/jem.172.2.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liew F. Y., Howard J. G., Hale C. Prophylactic immunization against experimental leishmaniasis. III. Protection against fatal Leishmania tropica infection induced by irradiated promastigotes involves Lyt-1+2- T cells that do not mediate cutaneous DTH. J Immunol. 1984 Jan;132(1):456–461. [PubMed] [Google Scholar]
  11. Mitchell G. F., Curtis J. M., Handman E., McKenzie I. F. Cutaneous leishmaniasis in mice: disease patterns in reconstituted nude mice of several genotypes infected with Leishmania tropica. Aust J Exp Biol Med Sci. 1980 Oct;58(5):521–532. doi: 10.1038/icb.1980.54. [DOI] [PubMed] [Google Scholar]
  12. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  13. Russell D. G., Alexander J. Effective immunization against cutaneous leishmaniasis with defined membrane antigens reconstituted into liposomes. J Immunol. 1988 Feb 15;140(4):1274–1279. [PubMed] [Google Scholar]
  14. Russell D. G., Wilhelm H. The involvement of the major surface glycoprotein (gp63) of Leishmania promastigotes in attachment to macrophages. J Immunol. 1986 Apr 1;136(7):2613–2620. [PubMed] [Google Scholar]
  15. Schumacher T. N., De Bruijn M. L., Vernie L. N., Kast W. M., Melief C. J., Neefjes J. J., Ploegh H. L. Peptide selection by MHC class I molecules. Nature. 1991 Apr 25;350(6320):703–706. doi: 10.1038/350703a0. [DOI] [PubMed] [Google Scholar]
  16. Scott P., Pearce E., Cheever A. W., Coffman R. L., Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. doi: 10.1111/j.1600-065x.1989.tb00557.x. [DOI] [PubMed] [Google Scholar]
  17. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  18. Yang D. M., Fairweather N., Button L. L., McMaster W. R., Kahl L. P., Liew F. Y. Oral Salmonella typhimurium (AroA-) vaccine expressing a major leishmanial surface protein (gp63) preferentially induces T helper 1 cells and protective immunity against leishmaniasis. J Immunol. 1990 Oct 1;145(7):2281–2285. [PubMed] [Google Scholar]
  19. Yang D. M., Rogers M. V., Liew F. Y. Identification and characterization of host-protective T-cell epitopes of a major surface glycoprotein (gp63) from Leishmania major. Immunology. 1991 Jan;72(1):3–9. [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES