Combined B cell and T cell epitopes

Abstract

Abstract B and T cell epitopes can either be overlapping or contiguous within a single sequence. Indeed, numerous studies have determined that up to, and within, a synthetic peptide sequence as small as ten amino acids, the B and T cell recognition sites may be distinct (1). Surface immunoglobulins are capable of binding to both linear sequences of amino acid residues and conformational epitopes which represent non-adjacent amino acid sequences brought into close proximity within a native protein, whereas the T cell receptor recognizes linear processed peptide epitopes bound to major histocompatibility complexes on molecules. B cells are among antigen-presenting cells capable of presenting peptide epitopes to CD4+ T cells. T cells produce cytokines and other immunomodulators that provide help for antibody production and induction of memory B cells. A single B and T cell epitope comprises the minimal built-in subunit able to trigger T and B cell co-operation in vivo (2). Moreover, studies have shown that overlapping B and T cell epitopes within a synthetic peptide sequence does not impair its B cell immunogenicity (3). The ability of a free synthetic peptide representing a single amino acid sequence, which varies minimally between strains, to act as a functional immunogen able to induce both long-lasting cellular and antibody responses has major implications for the design of future vaccines. Indeed, there exists numerous examples of peptides which are immunogenic in the free, uncoupled state. These results suggest that a satisfactory single sequence can readily induce full protection of all vaccinated animals against a severe challenge with the virulent parent virus (4, 5). Therefore, the topographical relationship between T and B cell epitopes within a native protein sequence is of great interest. This chapter describes experimental methods by which to identify combined and overlapping B and T cell epitopes within the same amino acid sequence with the aid of synthetic peptides.