SPECIFICITY VARIANTS IN MONOCLONAL-ANTIBODIES REACTIVE WITH PEPTIDE EPITOPES OF THE RING-INFECTED ERYTHROCYTE SURFACE-ANTIGEN (RESA) OF PLASMODIUM-FALCIPARUM

It has been suggested that repeat sequence antigens of Plasmodium falc iparum may serve the parasite in immune evasion by modifying the host antibody response and impairing the development of protective immunity . According to this proposal networks of cross-reactive, repeat sequen ce malarial antigens have the ability to stimulate a high proportion o f all somatically mutated B cells with altered antibody specificity, a nd thus to hinder the normal process of antibody affinity maturation. To determine the rate at which immunoglobulin mutations produce new re activities with repeat sequence antigens, hybridoma cell lines specifi c for the ring-infected erythrocyte surface antigen (RESA) were examin ed for the incidence of specificity variants that arose naturally or a s a result of treatment with the chemical mutagen ethylmethane sulphon ate (EMS). From one of the cell lines variants were readily isolated h aving reactivity towards a very closely related repeat sequence epitop e within the same RESA antigen. However, the other hybridoma/antigen c ombinations revealed no variants. In general, mutations giving rise to antibodies with altered specificity for related repetitive antigens w ere not readily induced and only limited support of the hypothesis was obtained.