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Improvement of the T-cell response to a non-immunogenic peptide by its tandem association with a highly efficient
F Rouaix1, H Gras-Masse, C Mazingue
1Unité mixte INSERM U167-CNRS 624, Institut Pasteur de Lille, France.
The 45-69 peptide, an helper T-cell epitope derived from HIV nef protein, is strongly immunogenic. A T-cell proliferative response was observed following immunization of Lou/M rats with 45-69 peptide administered 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 of 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) resulting from tandem synthesis of 115-131 and 45-69 peptides. A covalent association 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 respective tandem peptides (45-115 and 115-45) is critical for the T-cell response. These peptidic constructs possess distinct properties of antigenicity and immunogenicity but both allowed to reveal the existence of a 115-131 specific T-cell response normally undetectable using 115-131 peptide alone. This immunopharmacological approach should be useful in the rational design and construction of vaccines.
The 45-69 peptide, an helper T-cell epitope derived from HIV nef protein, is strongly immunogenic. A T-cell proliferative response was observed following immunization of Lou/M rats with 45-69 peptide administered 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 of 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) resulting from tandem synthesis of 115-131 and 45-69 peptides. A covalent association 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 respective tandem peptides (45-115 and 115-45) is critical for the T-cell response. These peptidic constructs possess distinct properties of antigenicity and immunogenicity but both allowed to reveal the existence of a 115-131 specific T-cell response normally undetectable using 115-131 peptide alone. This immunopharmacological approach should be useful in the rational design and construction of vaccines.