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

Cloned cytotoxic T cells recognize an epitope in the circumsporozoite protein and protect against... 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 protein1–4. 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 protection5. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells) 6,7, whose target is probably the developing liver-stage parasites8–10. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies11. 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 cells12,13. 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

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

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References (30)

Publisher
Springer Journals
Copyright
Copyright © 1989 by Nature Publishing Group
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/341323a0
Publisher site
See Article on Publisher Site

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 protein1–4. 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 protection5. This idea was supported by the recent observation that protective immunity also requires T-cells expressing the CDS antigen (CD8+ T cells) 6,7, whose target is probably the developing liver-stage parasites8–10. Moreover, an oral Salmonella vaccine that expresses the circumsporozoite protein is able to protect against murine malaria in the absence of antibodies11. 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 cells12,13. 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.

Journal

NatureSpringer Journals

Published: Sep 28, 1989

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