Evidence implicating MHC genes in the immunological nonresponsiveness to the plasmodium falciparum CS protein
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Date
1990
Journal Title
Journal ISSN
Volume Title
Publisher
Bulletin of the World Health Organization
Abstract
The circumsporozoite (CS) protein is a major candiate vaccine antigen for the sporozoite stage of malaria. Both cytotoxic T cells (CTL) and antibody specific for the CS protein are thought to be important in protection. By examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (MHC) are important for immune responsiveness. F1 mice between high antibody responders and low antibody responders are high antibody responders, suggesting that in this model immune suppressor genes do not control the immune response. Using synthetic peptides to map epitopes for CTL and helper T cells (which are important for the antibody response) we have shown that the T-cell epitopes are located in the polymorphic region of the protein, and we hypothesize that T cells have indeed selected the variation observed in the CS protein. The success of subunit vaccines will depend on the pattern of variation in different geographical locations, the ability to construct multivalent vaccines containing different variant epitopes from this protein, and on the existence of other sporozoite and liver-stage proteins involved in protection.
Description
Keywords
EMTREE drug terms: major histocompatibility antigen; malaria vaccine; parasite antigen, EMTREE medical terms: animal cell; conference paper; malaria; mouse; nonhuman; plasmodium falciparum; priority journal; sporozoite, MeSH: Animal; Antigens, CD4; Antigens, Protozoan; Antigens, Surface; Epitopes; Genes, MHC Class I; Lymphocyte Depletion; Mice; Plasmodium falciparum; T-Lymphocytes, Cytotoxic
Citation
Good, M. F., Kumar, S., De Groot, A. S., Weiss, W. R., Quakyi, I. A., Dontfraid, F., . . . Miller, L. H. (1990). Evidence implicating MHC genes in the immunological nonresponsiveness to the plasmodium falciparum CS protein. Bulletin of the World Health Organization, 68(SUPPL.), 80-84