Leishmania pifanoi amastigote antigen P-4: Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis

Jessica E. Haberer, Alda Maria Da-Cruz, Lynn Soong, Manoel P. Oliveira-Neto, Luis Rivas, Diane Mcmahon-Pratt, Sergio G. Coutinho

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16 Scopus citations

Abstract

In experimental murine cutaneous leishmaniasis, the purified Leishmania pifanoi amastigote protein P-4 has been shown to induce significant protection against infection. Further, recent studies examining the response of peripheral blood mononuclear cells (PBMC) from Leishmania braziliensis- infected human patients have demonstrated that the P-4 protein selectively elicits a significant T(H)1-like response. Because a T(H)1-like response is associated with cure, epitope studies were conducted to further evaluate the human response to P-4. PBMC from confirmed cutaneous leishmaniasis patients infected with L. braziliensis in Rio de Janeiro, Brazil, an area where the disease is endemic, were examined for T-cell proliferation and/or cytokine production in response to whole-parasite homogenate, isolated P-4 protein, and/or P-4 peptides. Twenty of the 22 patients (91%) examined responded to the native P-4 protein by proliferation and/or gamma interferon (IFN-γ) production. According to the proliferation data, PBMC from 14 patients (64%) were found to respond to the intact P-4 protein (stimulation index of ≤2.5). Fifty-seven percent of the P-4-responsive patients studied responded to at least one of the P-4 peptides; 11 individual peptides were found to elicit a proliferative response. Of 17 patients examined for cytokine production, no PBMC produced detectable interleukin-4 in response to P-4 protein or peptides. However, PBMC from 14 patients (82%) produced significant levels of IFN-γ (≤20 pg/ml) in response to native P-4 protein. Nineteen of the 23 peptides were found to elicit an IFN-γ response from at least two patients. These data indicate that multiple epitopes spanning the entire P-4 molecule are responsible for the T(H)1-like immune response observed, indicating that the intact P-4 amastigote molecule, rather than selected peptides, may prove to be the most useful for leishmaniasis vaccine development.

Original languageEnglish (US)
Pages (from-to)3100-3105
Number of pages6
JournalInfection and immunity
Volume66
Issue number7
DOIs
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Haberer, J. E., Da-Cruz, A. M., Soong, L., Oliveira-Neto, M. P., Rivas, L., Mcmahon-Pratt, D., & Coutinho, S. G. (1998). Leishmania pifanoi amastigote antigen P-4: Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis. Infection and immunity, 66(7), 3100-3105. https://doi.org/10.1128/iai.66.7.3100-3105.1998