This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Malik, A. Articles by Hoffman, S. L. Search for Related Content PubMed PubMed Citation Articles by Malik, A. Articles by Hoffman, S. L.

 Previous Article  |  Next Article 

Infect. Immun., 05 1995, 1955-1959, Vol 63, No. 5
Copyright © 1995, American Society for Microbiology

Identification of a nonameric H-2Kk-restricted CD8+ cytotoxic T lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein

A Malik, R Houghten, G Corradin, S Buus, JA Berzofsky and SL Hoffman
Malaria Program, Naval Medical Research Institute, Bethesda, Maryland 20889-5607, USA.

Class I-restricted CD8+ cytotoxic T lymphocytes (CTL) against the circumsporozoite protein (CSP) protect mice against the rodent malaria parasite, Plasmodium yoelii, and vaccines designed to produce protective CTL against the P. falciparum CSP (PfCSP) are under development. Humans and B10.BR (H-2k) mice have been shown to have CD8+ CTL activity against a 23-amino-acid region of the PfCSP (residues 368 to 390 from the PfCSP 7G8 sequence) that is too long to bind directly to class I major histocompatibility complex molecules. To identify within this 23-amino-acid peptide a shorter peptide that binds to an H- 2k class I major histocompatibility molecule, a primarily CD8+ (97.8%) T-cell line (PfCSP TCL.1) was produced by immunizing B10.BR mice with recombinant vaccinia virus expressing the PfCSP and stimulating in vitro spleen cells from these immunized mice with L cells transfected with the PfCSP gene (LPF cells). PfCSP TCL.1 lysed LPF cells and L cells pulsed with peptide PfCSP 7G8 368-390. When 15 overlapping nonamer peptides spanning the 368 to 390 sequence were tested, only one peptide, PfCSP 7G8 375-383 (Y E N D I E K K I), which includes an H-2Kk- binding motif, E at amino acid residue 2, and I at residue 9, sensitized targets for lysis by PfCSP TCL.1. Furthermore, a 10(3)- to 10(4)-fold lower concentration of the nonamer than that of the 23-amino- acid peptide was required to sensitize target cells for lysis by PfCSP TCL.1. Presentation by H-2Kk was demonstrated by using 3T3 fibroblast cells transfected with the murine H-2Kk or H-2Dk genes, and only the H- 2Kk transfectants were lysed by PfCSP TCL.1 after incubation with peptide PfCSP 7G8 375-383. Binding to H-2Kk was confirmed by competitive inhibition of binding of labelled peptides to affinity- purified Kk molecules. Substitution of the anchor amino acid residue, E, at position 2 with A dramatically reduced binding to Kk and eliminated the capacity of the peptide to sensitize target cells for killing. Variation of non-anchor residues did not markedly reduce binding to Kk but in some cases eliminated the capacity of the peptide to sensitize targets for cytolysis by PfCSP TCL.1, presumably by eliminating T-cell receptor-binding sites. These data suggest that similar studies with human T cells will be required for optimal development of peptide-based vaccines designed to produce protective class I-restricted CD8+ CTL against the PfCSP in humans.

This article has been cited by other articles:

• Garcia, J. E., Puentes, A., Patarroyo, M. E. (2006). Developmental Biology of Sporozoite-Host Interactions in Plasmodium falciparum Malaria: Implications for Vaccine Design. Clin. Microbiol. Rev. 19: 686-707 [Abstract] [Full Text]  
• Leggatt, G. R., Hosmalin, A., Pendleton, C. D., Kumar, A., Hoffman, S., Berzofsky, J. A. (1998). The Importance of Pairwise Interactions Between Peptide Residues in the Delineation of TCR Specificity. J. Immunol. 161: 4728-4735 [Abstract] [Full Text]  
• Miyahira, Y., Garcia-Sastre, A., Rodriguez, D., Rodriguez, J. R., Murata, K., Tsuji, M., Palese, P., Esteban, M., Zavala, F., Nussenzweig, R. S. (1998). Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice. Proc. Natl. Acad. Sci. USA 95: 3954-3959 [Abstract] [Full Text]