IMPROVEMENT OF THE T-CELL RESPONSE TO A NONIMMUNOGENIC PEPTIDE BY ITSTANDEM ASSOCIATION WITH A HIGHLY EFFICIENT T-HELPER PEPTIDE

The 45-69 peptide, an helper T-cell epitope derived from HIV nef prote in, is strongly immunogenic. A T-cell proliferative response was obser ved following immunization of Lou/M rats with 45-69 peptide administer ed in low dose and without any adjuvant. It is already known that the T-cell response to the 115-131 peptide of Sm28GST antigen, a protein o f the parasite Schistosoma mansoni, requires the presence of a carrier or the use of peptidic constructs. We demonstrate here that a T-cell response against the 115-131 peptide can be obtained in the absence of adjuvant using peptidic constructs (115-45 and 45-115 peptides) resul ting from tandem synthesis of 115-131 and 45-69 peptides. A covalent a ssociation of both peptides is necessary, since the co-injection of 45 -69 and 115-131 peptides is not sufficient to induce a detectable anti -115-131 T-cell response. The mutual orientation between the respectiv e tandem peptides (45-115 and 115-45) is critical for the T-cell respo nse. These peptidic constructs possess distinct properties of antigeni city and immunogenicity but both allowed to reveal the existence of a 115-131 specific T-cell response normally undetectable using 115-131 p eptide alone. This immunopharmacological approach should be useful in the rational design and construction of vaccines.