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.
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.
Quin
S J
SJ
National Institute for Medical Research, The Ridgeway, Mill Hill, London, GB.
Seixas
E M
EM
Cross
C A
CA
Berg
M
M
Lindo
V
V
Stockinger
B
B
Langhorne
J
J
D000478:Alkylation; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006825:Hybridomas / Q000276:immunology; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology*; D016788:Plasmodium chabaudi / Q000276:immunology*; D013997:Time Factors
D000913:Antibodies, Protozoan; D000949:Histocompatibility Antigens Class II; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments