Different regions of the malaria merozoite surface protein 1 of Plasmodium chabaudi elicit distinct T-cell and antibody isotype responses.
In this study we have investigated the antibody and CD4 T-cell responses to the well-characterized malaria vaccine candidate MSP-1 during the course of a primary Plasmodium chabaudi chabaudi (AS) infection. Specific antibody responses can be detected within the first week of infection, and CD4 T cells can be detected after 3 weeks of infection. The magnitude of the CD4 T-cell response elicited during a primary infection depended upon the region of MSP-1. In general, the highest precursor frequencies were obtained when a recombinant MSP-1 fragment corresponding to amino acids 900 to 1507 was used as the antigen in vitro. By contrast, proliferative and cytokine responses against amino acids 1508 to 1766 containing the C-terminal 21-kDa region of the molecule were low. The characteristic interleukin 4 (IL-4) switch that occurs in the CD4 T-cell population after an acute blood stage P. c. chabaudi infection was only consistently observed in the response to the amino acid 900 to 1507 MSP1 fragment. A lower frequency of IL-4-producing cells was seen in response to other regions. Although the magnitudes of the immunoglobulin G antibody responses to the different regions of MSP-1 were similar, the isotype composition of each response was distinct, and there was no obvious relationship with the type of T helper cells generated. Interestingly, a relatively high antibody response to the C-terminal region of MSP-1 was observed, suggesting that T-cell epitopes outside of this region may provide the necessary cognate help for specific antibody production.
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, United Kingdom.
S J
SJ
Quin
J
J
Langhorne
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000097:blood*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016788:Plasmodium chabaudi / Q000276:immunology*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D020066:Merozoite Surface Protein 1; D015847:Interleukin-4; D007371:Interferon-gamma