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).