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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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
StatePublished - Jul 1998
Externally publishedYes

Fingerprint

Cutaneous Leishmaniasis
Leishmania
Epitopes
T-Lymphocytes
Antigens
Blood Cells
Leishmania braziliensis
Proteins
Peptides
Interferons
Leishmaniasis Vaccines
Cytokines
Endemic Diseases
Interleukin-4
Interferon-gamma
Brazil
Parasites
Cell Proliferation
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

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.

Leishmania pifanoi amastigote antigen P-4 : Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis. / Haberer, Jessica E.; Da-Cruz, Alda Maria; Soong, Lynn; Oliveira-Neto, Manoel P.; Rivas, Luis; Mcmahon-Pratt, Diane; Coutinho, Sergio G.

In: Infection and Immunity, Vol. 66, No. 7, 07.1998, p. 3100-3105.

Research output: Contribution to journalArticle

Haberer, JE, Da-Cruz, AM, Soong, L, Oliveira-Neto, MP, Rivas, L, Mcmahon-Pratt, D & Coutinho, SG 1998, 'Leishmania pifanoi amastigote antigen P-4: Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis', Infection and Immunity, vol. 66, no. 7, pp. 3100-3105.
Haberer JE, Da-Cruz AM, Soong L, Oliveira-Neto MP, Rivas L, Mcmahon-Pratt D et al. Leishmania pifanoi amastigote antigen P-4: Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis. Infection and Immunity. 1998 Jul;66(7):3100-3105.
Haberer, Jessica E. ; Da-Cruz, Alda Maria ; Soong, Lynn ; Oliveira-Neto, Manoel P. ; Rivas, Luis ; Mcmahon-Pratt, Diane ; Coutinho, Sergio G. / Leishmania pifanoi amastigote antigen P-4 : Epitopes involved in T-cell responsiveness in human cutaneous leishmaniasis. In: Infection and Immunity. 1998 ; Vol. 66, No. 7. pp. 3100-3105.
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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.",
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