Institut National De La Sante Et De La Recherche Medicale

Institut Gustave Roussy

Centre National De La Recherche Scientifique

Genethon

David Alexandre Gross

Kostas Kosmatopoulos

Sophie Tourdot

Antonio Scardino

Identifying subdominant/cryptic epitopes (I) that are presented by a HLA (human leukocyte antigen) Class I molecule, is new. Identifying subdominant/cryptic epitopes (I) that are presented by a HLA (human leukocyte antigen) Class I molecule comprising selecting at least one peptide (II) of 8-11 amino acids (aa), potentially representing an epitope for Class I presentation, from a protein against which a cytotoxic T cell (CTL) response is to be raised. (II) corresponds to a non-immunogenic peptide with low affinity for Class I molecules. Variants (IIa) of (II) are prepared in which the N-terminal aa is replaced by Tyr and their immunogenicity detected by identifying those that generate a CTL response against target cells expressing the parent protein. Peptide sequences from which active (IIa) are derived are then identified. Independent claims are also included for the following: (1) immunogenic peptide epitopes (IIa) derived from (I) identified this way; and (2) nucleic acid (III) that encodes chimeric polypeptides (IV) containing one or more, same or different, copies of (IIa).

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Paris, France

David Alexandre Gross