BINDING OF MALARIA T-CELL EPITOPES TO DR AND DQ MOLECULES IN-VITRO CORRELATES WITH IMMUNOGENICITY IN-VIVO - IDENTIFICATION OF A UNIVERSAL T-CELL EPITOPE IN THE PLASMODIUM-FALCIPARUM CIRCUMSPOROZOITE PROTEIN

The efficacy of a malaria peptide vaccine would be enhanced by the inc lusion of a parasite-derived universal T cell epitope to ensure that a ll vaccinees develop parasite-specific cellular and humoral immunity, Two circumsporozoite (CS) protein T cell epitopes, previously identifi ed by CD4(+) T cell clones derived from Plasmodium falciparum sporozoi te-immunized volunteers, were studied to determine their HLA class II binding potential, One epitope, located in amino acid (aa) 326-345 of the P, falciparum (NF54 strain) CS protein, was ''universal'' in that it could bind to multiple DR acid DQ molecules in vitro, in contrast, the second epitope, T1, which is located in the CS repeat region, tvas recognized by T cells in the context of DQ6 (DQB10603) and did not b ind with high affinity to any of the class II molecules tested in the peptide binding assays, The in vitro patterns of peptide/HLA interacti ons correlated with immunogenicity in vivo, A multiple antigen peptide (MAP) containing the aa 326-345 epitope elicited responses in eight i nbred strains (H2(a,b,d,k,p,q,r,s)), while the T1 MAP was recognized by only a single haplotype, H-2(b), The combination of the universal a a 326-345 T cell epitope and the T1 repeat in a di-epitope MAP overcam e the genetic restriction to the P, falciparum CS repeat region and el icited antisporozoite Ab responses in all of the MAP-immunized mice, S ynthetic peptide malaria vaccines containing the aa 326-345 universal T cell epitope would be expected to elicit parasite-specific immune re sponses in both sporozoite-primed and naive individuals of diverse gen etic backgrounds.