This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rathore, D.
Right arrow Articles by McCutchan, T. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rathore, D.
Right arrow Articles by McCutchan, T. F.

 Previous Article  |  Next Article 

Infection and Immunity, February 2000, p. 740-743, Vol. 68, No. 2
0019-9567/00/$04.00+0

The Cytotoxic T-Lymphocyte Epitope of the Plasmodium falciparum Circumsporozoite Protein Also Modulates the Efficiency of Receptor-Ligand Interaction with Hepatocytes

Dharmendar Rathore and Thomas F. McCutchan*

Growth and Development Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425

Received 3 August 1999/Returned for modification 9 September 1999/Accepted 2 November 1999

Malaria sporozoites are transmitted from the mosquito salivary gland to host hepatocytes within minutes of an infectious bite. The circumsporozoite protein (CS), which covers the surface of Plasmodium sporozoites, functions during these minutes in the targeting of host liver cells. The protein's potentially important role in an antimalaria vaccine has spawned interest in both the host immune responses to the parasite's presence and the actual functional role of the protein in the targeting of host liver cells. Here we show that the region of CS known to elicit a cytotoxic T-lymphocyte (CTL) response to irradiated sporozoites also, somewhat ironically, mediates the receptor-ligand interaction essential to parasite invasion of the host. Hence, the structure of CS represents a balance of potentially counterdirectional forces. Polymorphism in the CTL epitope appears to be a product of this balanced state as opposed to an "arms race" as it is so often portrayed. The conceptual difference between the theories regarding the maintainance of polymorphism in CTL epitopes may have significant implication for vaccine design.

* Corresponding author. Mailing address: Rm. 126, Bldg. 4, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Dr., MSC 0425, Bethesda, MD 20892-0425. Phone: (301) 496-6149. Fax: (301) 402-0079. E-mail: Tmccutchan{at}niaid.nih.gov.

Infection and Immunity, February 2000, p. 740-743, Vol. 68, No. 2
0019-9567/00/$04.00+0


This article has been cited by other articles:

  • Chinchilla, M., Pasetti, M. F., Medina-Moreno, S., Wang, J. Y., Gomez-Duarte, O. G., Stout, R., Levine, M. M., Galen, J. E. (2007). Enhanced Immunity to Plasmodium falciparum Circumsporozoite Protein (PfCSP) by Using Salmonella enterica Serovar Typhi Expressing PfCSP and a PfCSP-Encoding DNA Vaccine in a Heterologous Prime-Boost Strategy. Infect. Immun. 75: 3769-3779 [Abstract] [Full Text]  
  • Jalloh, A., van Thien, H., Ferreira, M. U., Ohashi, J., Matsuoka, H., Kanbe, T., Kikuchi, A., Kawamoto, F. (2006). Sequence Variation in the T-Cell Epitopes of the Plasmodium falciparum Circumsporozoite Protein among Field Isolates Is Temporally Stable: a 5-Year Longitudinal Study in Southern Vietnam. J. Clin. Microbiol. 44: 1229-1235 [Abstract] [Full Text]  
  • Kumkhaek, C., Phra-ek, K., Renia, L., Singhasivanon, P., Looareesuwan, S., Hirunpetcharat, C., White, N. J., Brockman, A., Gruner, A. C., Lebrun, N., Alloueche, A., Nosten, F., Khusmith, S., Snounou, G. (2005). Are Extensive T Cell Epitope Polymorphisms in the Plasmodium falciparum Circumsporozoite Antigen, a Leading Sporozoite Vaccine Candidate, Selected by Immune Pressure?. J. Immunol. 175: 3935-3939 [Abstract] [Full Text]  
  • Rathore, D., Nagarkatti, R., Jani, D., Chattopadhyay, R., de la Vega, P., Kumar, S., McCutchan, T. F. (2005). An Immunologically Cryptic Epitope of Plasmodium falciparum Circumsporozoite Protein Facilitates Liver Cell Recognition and Induces Protective Antibodies That Block Liver Cell Invasion. J. Biol. Chem. 280: 20524-20529 [Abstract] [Full Text]  
  • Rathore, D., Hrstka, S. C. L., Sacci, J. B. Jr., De la Vega, P., Linhardt, R. J., Kumar, S., McCutchan, T. F. (2003). Molecular Mechanism of Host Specificity in Plasmodium falciparum Infection: ROLE OF CIRCUMSPOROZOITE PROTEIN. J. Biol. Chem. 278: 40905-40910 [Abstract] [Full Text]  
  • Chattopadhyay, R., Rathore, D., Fujioka, H., Kumar, S., de la Vega, P., Haynes, D., Moch, K., Fryauff, D., Wang, R., Carucci, D. J., Hoffman, S. L. (2003). PfSPATR, a Plasmodium falciparum Protein Containing an Altered Thrombospondin Type I Repeat Domain Is Expressed at Several Stages of the Parasite Life Cycle and Is the Target of Inhibitory Antibodies. J. Biol. Chem. 278: 25977-25981 [Abstract] [Full Text]  
  • Rathore, D., Sacci, J. B., de la Vega, P., McCutchan, T. F. (2002). Binding and Invasion of Liver Cells by Plasmodium falciparum Sporozoites. ESSENTIAL INVOLVEMENT OF THE AMINO TERMINUS OF CIRCUMSPOROZOITE PROTEIN. J. Biol. Chem. 277: 7092-7098 [Abstract] [Full Text]  
  • Rathore, D., McCutchan, T. F. (2000). Role of cysteines in Plasmodium falciparum circumsporozoite protein: Interactions with heparin can rejuvenate inactive protein mutants. Proc. Natl. Acad. Sci. USA 10.1073/pnas.140224597v1 [Abstract] [Full Text]  
  • Rathore, D., McCutchan, T. F. (2000). Role of cysteines in Plasmodium falciparum circumsporozoite protein: Interactions with heparin can rejuvenate inactive protein mutants. Proc. Natl. Acad. Sci. USA 97: 8530-8535 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»