A CRYPTIC T-CELL EPITOPE ON THE APICAL MEMBRANE ANTIGEN-1 OF PLASMODIUM-CHABAUDI-ADAMI CAN PRIME FOR AN ANAMNESTIC ANTIBODY-RESPONSE - IMPLICATIONS FOR MALARIA VACCINE DESIGN

We have investigated the proliferative and Th cell responses to the Pl asmodium chabaudi adami DS homologue of the Plasmodium falciparum apic al membrane Ag 1 (AMA-1), a leading malaria vaccine candidate, Immunod ominant T cell epitopes were defined following immunization of BALB/c mice with Escherichia coli-expressed, refolded P. c. adami DS AMA-1 re combinant protein and testing cells from the draining lymph nodes for responses against a series of overlapping peptides spanning P. c. adam i AMA-1, A limited number of major T cell sites were identified in bot h conserved and variable regions of the protein, Several cryptic epito pes that evoked T cell responses following immunization with peptides, but not after protein immunization, were also identified, Adoptive tr ansfer of a T cell line specific for a conserved cryptic epitope (corr esponding to residues 31-50) provided help for an anti-AMA-1 protein-s pecific Ab response following in vivo challenge with P. c. adami paras itized RBC, such that AMA-1-specific Abs appeared more rapidly in reci pient mice than in controls, Furthermore, T cells specific for cryptic epitopes afforded partial protection against P. c. adami infection in nude mice, The identification of conserved cryptic Th cell epitopes h as important implications for malaria vaccine design.