Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei

P. J. Romero, J. P. Tam, D. Schlesinger, P. Clavijo, H. Gibson, P. J. Barr, R. S. Nussenzweig, V. Nussenzweig, Fidel P Zavala

Research output: Contribution to journalArticle

Abstract

The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2(j) mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2(j) mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observzations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.

Original languageEnglish (US)
Pages (from-to)1951-1957
Number of pages7
JournalEuropean Journal of Immunology
Volume18
Issue number12
StatePublished - 1988
Externally publishedYes

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Plasmodium berghei
T-Lymphocyte Epitopes
Sporozoites
Proteins
B-Lymphocyte Epitopes
Peptides
Haplotypes
Antibody Formation
Peptide T
Synthetic Vaccines
Humoral Immunity
Epitopes
Anti-Idiotypic Antibodies
Immunization
Polymers
Yeasts
Lymph Nodes
Injections
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Romero, P. J., Tam, J. P., Schlesinger, D., Clavijo, P., Gibson, H., Barr, P. J., ... Zavala, F. P. (1988). Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. European Journal of Immunology, 18(12), 1951-1957.

Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. / Romero, P. J.; Tam, J. P.; Schlesinger, D.; Clavijo, P.; Gibson, H.; Barr, P. J.; Nussenzweig, R. S.; Nussenzweig, V.; Zavala, Fidel P.

In: European Journal of Immunology, Vol. 18, No. 12, 1988, p. 1951-1957.

Research output: Contribution to journalArticle

Romero, PJ, Tam, JP, Schlesinger, D, Clavijo, P, Gibson, H, Barr, PJ, Nussenzweig, RS, Nussenzweig, V & Zavala, FP 1988, 'Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei', European Journal of Immunology, vol. 18, no. 12, pp. 1951-1957.
Romero PJ, Tam JP, Schlesinger D, Clavijo P, Gibson H, Barr PJ et al. Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. European Journal of Immunology. 1988;18(12):1951-1957.
Romero, P. J. ; Tam, J. P. ; Schlesinger, D. ; Clavijo, P. ; Gibson, H. ; Barr, P. J. ; Nussenzweig, R. S. ; Nussenzweig, V. ; Zavala, Fidel P. / Multiple T helper cell epitopes of the circumsporozoite protein of Plasmodium berghei. In: European Journal of Immunology. 1988 ; Vol. 18, No. 12. pp. 1951-1957.
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AU - Romero, P. J.

AU - Tam, J. P.

AU - Schlesinger, D.

AU - Clavijo, P.

AU - Gibson, H.

AU - Barr, P. J.

AU - Nussenzweig, R. S.

AU - Nussenzweig, V.

AU - Zavala, Fidel P

PY - 1988

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N2 - The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2(j) mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2(j) mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observzations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.

AB - The present findings establish the lack of genetic restriction of the humoral immune response to sporozoites of Plasmodium berghei, corraborating earlier observations that mice of different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti-sporozoite antibodies are directed against the repetitive B cell epitope of the circumsporozoite (CS) protein. However, neither a peptide containing a dimer of this repeat (17.1), nor a peptide polymer containing multiple repeats induced an antibody response in mice of different H-2 and different genetic backgrounds. A yeast-derived recombinant, containing the repeat domain and part of the surrounding amino and carboxy-terminal regions of the P. berghei CS protein, induces very different levels of antibody in mice of diverse H-2 haplotypes. H-2(j) mice are high responders and the immunized mice are extensively protected against sporozoite challenge. The lymph node cells of the H-2(j) mice (but not from other strains) proliferated in the presence of peptide N, contained in the amino terminal region of the CS recombinant. Additional H-2-restricted T cell epitopes have been identified in amino and carboxy-terminal regions of the CS protein, and mice of most of the strains recognized multiple T cell epitopes. Two peptides representing T cell epitopes were synthesized in tandem with a peptide representing the B cell epitope, and were assayed for T helper activity in vivo. The antibody response of mice, primed by a single injection of sporozoites, was boosted very effectively by the administration of peptide N + 17.1 or peptide B-4 + 17.1. The B-4 T cell epitope is located in the carboxy-terminal region of the CS protein and is recognized by mice of at least four different H-2 haplotypes. These observzations demonstrate that the immune response to the CS protein of P. berghei is not genetically restricted and that it contains several T cell epitopes, some of which can function as helper epitopes. In addition, they show that a synthetic sporozoite vaccine can boost the immune response to sporozoites.

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