Identification of T epitopes within a potential Plasmodium falciparum vaccine antigen: A study of human lymphocyte responses to repeat and nonrepeat regions of Pf155/RESA

PBMC from Melanesians who had high antibody reactivities to fusion protein encompassing the 3' and the 5' repeat regions of the ring infected E surface antigen (Pf155/RESA), were tested for their ability to respond to synthetic and recombinant peptides representing regions of Pf155/RESA. The aim was to identify T cell epitopes within the Ag. Most of the synthetic peptides from the nonrepeat regions of Pf155/RESA were selected for study on the basis of their tendency to form amphipathic α-helices. Peptides representing immunodominant B cell epitopes were also tested. Three-quarters of the Melanesian donors responded to the recombinant peptides (Ag 1505 and Ag 632-100) and to the 8 x 4 mer, a synthetic peptide representative of the 3' repeat region. Whereas all the remaining eight peptides tested elicited a response in at least one donor, three peptides (M40, M42, and BTA3) representing sequences in the nonrepeat regions showed greatest promise as potentially useful T epitopes. Responses in control donors were also observed to most of the peptides but the percentage of responders was lower. T cell bulk lines specific to Ag 1505 and Ag 632-100 were established. All donors were HLA tissue typed, but no obvious correlations between responsiveness and HLA type were observed. Our results suggest that there are T cell epitopes within and outside the repeat regions of Pf155/RESA.