Low CD4(+) T cell responses to the C-terminal region of the malaria merozoite surface protein-1 may be attributed to processing within distinct MHC class II pathways

Eur J Immunol. 2001 Jan;31(1):72-81. doi: 10.1002/1521-4141(200101)31:1<72::aid-immu72>3.0.co;2-z.

Abstract

The C-terminal fragment of merozoite surface protein-1 (MSP-1) of the mouse malaria parasite Plasmodium chabaudi chabaudi (AS) stimulates a weak CD4 T cell response when compared to the response to a more structurally simple region of the molecule. The tertiary structure of the C-terminal region of MSP-1 is maintained by five disulfide bonds. A peptide from this region could only be processed and loaded onto newly synthesized MHC class II molecules, whereas a peptide from the structurally simple region was available for loading onto recycling MHC class II. CD4(+) T cell hybridomas took longer to recognize an epitope derived from the disulfide-bonded region whether native parasite or recombinant MSP-1 antigen was used. Reduction of disulfide bonds in the C-terminal region subsequently allowed peptides to be loaded onto recycling MHC class II and greatly enhanced the rapidity of the T cell response. These data demonstrate that differential processing occurs intramolecularly in MSP-1, which may be responsible for the observed weak CD4 T cell responses against this region. The consequences of this in vivo may be that limited T cell help is available for protective antibody production which has important implications for designing vaccines based on MSP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Animals
  • Antibodies, Protozoan / biosynthesis
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes / immunology*
  • Female
  • Histocompatibility Antigens Class II / physiology*
  • Hybridomas / immunology
  • Merozoite Surface Protein 1 / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / immunology*
  • Plasmodium chabaudi / immunology*
  • Time Factors

Substances

  • Antibodies, Protozoan
  • Histocompatibility Antigens Class II
  • Merozoite Surface Protein 1
  • Peptide Fragments