Human T-Cell Recognition of the Circumsporozoite Protein of Plasmodium falciparum: Immunodominant T-Cell Domains Map to the Polymorphic Regions of the Molecule

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 4; pp. 1199 - 1203
• Main Authors: Good, Michael F., Pombo, David, Quakyi, Isabella A., Riley, Eleanor M., Houghten, Richard A., Menon, Arun, Alling, David W., Berzofsky, Jay A., Miller, Louis H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.02.1988; National Acad Sciences
• Subjects: Adult; Aged; Animals; Antibodies; Antigens, Protozoan - genetics; Antigens, Protozoan - immunology; Antigens, Surface - genetics; Antigens, Surface - immunology; Biochemistry. Physiology. Immunology. Molecular biology; Biological and medical sciences; Blood; Epitopes; Epitopes - genetics; Epitopes - immunology; Female; Fundamental and applied biological sciences. Psychology; Human protozoal diseases; Humans; Immunodominant epitopes; Infectious diseases; Lymphocyte Activation; Lymphocytes; Malaria; Male; Medical sciences; Middle Aged; Molecules; Parasites; Parasitic diseases; Peptide Fragments - chemical synthesis; Peptide Fragments - immunology; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Polymorphism, Genetic; Protozoa; Protozoal diseases; Protozoan Proteins; Sporozoites; T lymphocyte epitopes; T lymphocytes; T-Lymphocytes - immunology; Tropical medicine; Human; Protozoa; Protozoal disease; Immune response; Malaria; Biological evolution; Cellular immunity; Sporozoit; Vaccine; Immunodominance; Infection; Proteins; Plasmodium falciparum; Immunology; T-Lymphocyte; Mutation; Sporozoa; Polymorphism
• DOI: 10.1073/pnas.85.4.1199
• ISSN: 0027-8424

The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent T-cell immunity. To identify such sites on the circumsporozoite (CS) protein of Plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire CS protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a P. falciparum malaria-endemic region of West Africa. Three immunodominant domains were located outside the repetitive region. These domains, however, occurred in the polymorphic regions of the molecule, suggesting that parasite mutation and selection has occurred in response to immune pressure from T cells. Such polymorphism may impose an obstacle for vaccine development.