Immunogenicity of multiple antigen peptides (MAP) containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite protein

Eur J Immunol. 1991 Dec;21(12):3015-20. doi: 10.1002/eji.1830211217.

Abstract

The immunogenicity of multiple antigen peptides (MAP) constructs containing T and B cell epitopes of the repeat region of the P. falciparum circumsporozoite (CS) protein was examined in vitro, using a human T cell clone, and in vivo, using four different strains of mice. All the MAP constructs that contained the T cell epitope, (DPNANPNVDPNANPNV), stimulated proliferation and interferon-gamma production by a human T cell clone specific for this epitope which is located in the 5' end of the repeat region of the P. falciparum CS protein. These human T cells did not recognize MAP that contained only the B cell epitope, (NANP)3, which is located in the 3' repeat region. Optimal antibody responses were obtained in mice immunized with MAP containing four copies of tandemly arranged T and B cell epitopes, (TB)4. The murine immune response to the MAP constructs was genetically restricted. Mice of a high responder strain, C57BL, recognized both the 5' and 3' repeat sequences in the MAP as T, as well as B, cell epitopes and developed very high anti-MAP and anti-sporozoite antibody titers. A/J and C3H mice, which were intermediate responders, developed lower antibody titers which varied according to the orientation of the T vs. the B cell epitopes within the MAP constructs. BALB/c mice were nonresponders and did not develop antibodies following immunization with any of the MAP constructs containing the 5' and 3' repeats of the P. falciparum CS protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antibody Formation
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology*
  • B-Lymphocytes / immunology*
  • Dose-Response Relationship, Immunologic
  • Epitopes
  • Humans
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • Plasmodium falciparum / immunology*
  • Protozoan Proteins / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes
  • Peptides
  • Protozoan Proteins
  • circumsporozoite protein, Protozoan