T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4 ؉ T cells expand and produce interferon ␥ (IFN-␥) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4 ؉ cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malariaspecific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine.
IntroductionT helper cells are essential for a protective immune response to the blood stages of the rodent malaria parasite, Plasmodium chabaudi chabaudi (AS). 1 There is debate, however, over the extent to which T cells protect via Th1 cytokine-mediated mechanisms or by the antibodies that they help to produce. Both mechanisms dominate the T-cell response to P chabaudi in turn, with an early Th1-type cytokine response, which switches later in infection to one that provides effective help for malaria-specific antibody production and produces less interferon ␥ (IFN-␥). 2,3 Increased T-helper cell activity in the later stages 3 is clearly beneficial because experiments in B cell-deficient mice demonstrate that B cells and antibodies are required for complete clearance of parasites, 4-6 although the requirements and specificity of T-cell help and antibody for rapid clearance or immunity to reinfection are not known.To determine the precise role of malaria-specific T helper cells and the potential of an important vaccine antigen, merozoite surface protein 1 (MSP-1), in the protection from and clearance of malaria infection, we have generated a T-cell receptor (TCR) transgenic mouse with a TCR specific for P chabaudi MSP-1. This molecule is expressed on the invasive merozoite surface, 7 and its C-terminal domain can induce a protective immune response. [8][9][10][11] However, this domain is not efficiently processed by antigenpresenting cells and is a less effective inducer of CD4 ϩ T-cell responses than other parts of MSP-1. 10,12,13 For more effective vaccination strategies it would be important to know whether CD4 ϩ T-cell help can be generated from other parts of MSP-1, which are more readily processed and presented on antigenpresenting cells. The MSP-1-specific TCR of our transgenic mouse,...
