Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria

Pedro Romero, Janet L. Maryanski, Giampietro Corradin, Ruth S. Nussenzweig, Victor Nussenzweig, Fidel P Zavala

Research output: Contribution to journalArticle

Abstract

PROTECTIVE immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly against the repeat domain of the circumsporozoite protein. Early experiments showed, however, that B-cell-depleted mice that are immunized with sporozoites can resist challenge, indicating that T-cell effector mechanisms may also have a role in protection. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells), whose target is probably the developing liver-stage parasites. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies. Here we report the identification of an epitope contained within amino acids 249-260 of the Plasmodium berghei circumsporozoite protein that is recognized by H-2Kd-restricted cytotoxic T cells. Passive transfer into mice of cytotoxic-T-cell clones that recognize this epitope conferred a high degree of protection against challenge. These results provide the first direct evidence that CD8+ T cells that are specific for a defined epitope can confer protection against a parasitic infection.

Original languageEnglish (US)
Pages (from-to)323-326
Number of pages4
JournalNature
Volume341
Issue number6240
StatePublished - 1989
Externally publishedYes

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T-Lymphocyte Epitopes
Malaria
T-Lymphocytes
Epitopes
Immunity
Sporozoites
Proteins
Salmonella Vaccines
CD8 Antigens
Plasmodium berghei
Parasitic Diseases
Neutralizing Antibodies
Parasites
Vaccination
B-Lymphocytes
Clone Cells
Amino Acids
Antibodies
Liver

ASJC Scopus subject areas

  • General

Cite this

Romero, P., Maryanski, J. L., Corradin, G., Nussenzweig, R. S., Nussenzweig, V., & Zavala, F. P. (1989). Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature, 341(6240), 323-326.

Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. / Romero, Pedro; Maryanski, Janet L.; Corradin, Giampietro; Nussenzweig, Ruth S.; Nussenzweig, Victor; Zavala, Fidel P.

In: Nature, Vol. 341, No. 6240, 1989, p. 323-326.

Research output: Contribution to journalArticle

Romero, P, Maryanski, JL, Corradin, G, Nussenzweig, RS, Nussenzweig, V & Zavala, FP 1989, 'Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria', Nature, vol. 341, no. 6240, pp. 323-326.
Romero P, Maryanski JL, Corradin G, Nussenzweig RS, Nussenzweig V, Zavala FP. Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. Nature. 1989;341(6240):323-326.
Romero, Pedro ; Maryanski, Janet L. ; Corradin, Giampietro ; Nussenzweig, Ruth S. ; Nussenzweig, Victor ; Zavala, Fidel P. / Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against malaria. In: Nature. 1989 ; Vol. 341, No. 6240. pp. 323-326.
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N2 - PROTECTIVE immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly against the repeat domain of the circumsporozoite protein. Early experiments showed, however, that B-cell-depleted mice that are immunized with sporozoites can resist challenge, indicating that T-cell effector mechanisms may also have a role in protection. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells), whose target is probably the developing liver-stage parasites. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies. Here we report the identification of an epitope contained within amino acids 249-260 of the Plasmodium berghei circumsporozoite protein that is recognized by H-2Kd-restricted cytotoxic T cells. Passive transfer into mice of cytotoxic-T-cell clones that recognize this epitope conferred a high degree of protection against challenge. These results provide the first direct evidence that CD8+ T cells that are specific for a defined epitope can confer protection against a parasitic infection.

AB - PROTECTIVE immunity against malaria is induced by vaccination of hosts with irradiation-attenuated sporozoites. This immunity is mediated in part by neutralizing antibodies that are directed mainly against the repeat domain of the circumsporozoite protein. Early experiments showed, however, that B-cell-depleted mice that are immunized with sporozoites can resist challenge, indicating that T-cell effector mechanisms may also have a role in protection. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells), whose target is probably the developing liver-stage parasites. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies. Here we report the identification of an epitope contained within amino acids 249-260 of the Plasmodium berghei circumsporozoite protein that is recognized by H-2Kd-restricted cytotoxic T cells. Passive transfer into mice of cytotoxic-T-cell clones that recognize this epitope conferred a high degree of protection against challenge. These results provide the first direct evidence that CD8+ T cells that are specific for a defined epitope can confer protection against a parasitic infection.

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