The objectives of this contract are to produce analogues of the selected conserved T cell epitopes that have been defined by altering amino acid sequences of the peptides aided by molecular/functional modeling of HLA class II binding grooves; assess the ability of each peptide analogue to bind to HLA-DR and -DQ molecules by determining the amount of biotinylated peptide which binds to sa set of murine L cells transfected with HLA-DR and DQ genes; evaluate analogues that bind to a larger number of HLA-DR or -DQ allelic products with equal or higher affinity than the original peptides for their ability to stimulate a recall proliferative response in African adults residing in an area where malaria is endamic. T cell cytokine responses will also be assessed in this population; and to immunize H-2 congenic mice with the peptide analogues and assess the quality and level of antimalarial antibody produced in vivo following exposure to P. falciparum parasites.
