Co-dominant and reciprocal T-helper cell activity of epitopic sequences and formation of junctional B-cell determinants in synthetic T:B chimeric immunogens.

Abstract

The identification of defined T-helper (Th) cell determinants, particularly those recognized in the context of several MHC or HLA haplotypes, and their use to provide effective carrier help to short synthetic constructs representing a B-cell epitope have made it feasible to synthesize putatively potent immunogens. However, a number of crucial questions regarding immunogenicity of epitopic sequences need to be addressed before an optimally effective synthetic vaccine can be designed. The present study deals with the hybrid constructs incorporating a known B-cell epitope from the merozoite surface protein-1 (MSP-1) of a human malarial parasite, Plasmodium falciparum, and the promiscuous Th-cell epitope from tetanus toxin or from the circumsporozoite protein of P. falciparum. Here, we provide data which suggest that B- and T-cell determinants present in a hybrid construct could, in fact, provide reciprocal helper activity for antibody production; that antibodies to a Th-cell epitope may not necessarily block its helper function; and that junctional B-cell epitopes may be formed. All this may influence, in an unpredictable manner, the quality of protective immune response sought to be generated using the chimeric immunogens, with important implications for vaccine design.