Human T-Cell Recognition of the Circumsporozoite Protein of Plasmodium falciparum: Immunodominant T-Cell Domains Map to the Polymorphic Regions of the Molecule
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 Plasmodiu...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 85; no. 4; pp. 1199 - 1203 |
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Main Authors | , , , , , , , , |
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 | |
Online Access | Get full text |
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Abstract | 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. |
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AbstractList | 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. The definition of human T-cell antigenic sites is important for subunit vaccine development of a peptide immunogen. 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 cell. |
Author | Berzofsky, Jay A. Menon, Arun Quakyi, Isabella A. Pombo, David Alling, David W. Miller, Louis H. Good, Michael F. Houghten, Richard A. Riley, Eleanor M. |
Author_xml | – sequence: 1 givenname: Michael F. surname: Good fullname: Good, Michael F. – sequence: 2 givenname: David surname: Pombo fullname: Pombo, David – sequence: 3 givenname: Isabella A. surname: Quakyi fullname: Quakyi, Isabella A. – sequence: 4 givenname: Eleanor M. surname: Riley fullname: Riley, Eleanor M. – sequence: 5 givenname: Richard A. surname: Houghten fullname: Houghten, Richard A. – sequence: 6 givenname: Arun surname: Menon fullname: Menon, Arun – sequence: 7 givenname: David W. surname: Alling fullname: Alling, David W. – sequence: 8 givenname: Jay A. surname: Berzofsky fullname: Berzofsky, Jay A. – sequence: 9 givenname: Louis H. surname: Miller fullname: Miller, Louis H. |
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Title | Human T-Cell Recognition of the Circumsporozoite Protein of Plasmodium falciparum: Immunodominant T-Cell Domains Map to the Polymorphic Regions of the Molecule |
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