IMMUNOGENICITY AND CROSS-REACTIVITY WITH IDIOTYPIC IGA OF VH CDR3 PEPTIDE IN MULTIPLE-MYELOMA

Multiple myeloma idiotypic protein is clone-specific and therefore rep resents an ideal tumour antigen for immune targeting. In this study we determined whether a synthetic peptide corresponding to the autologou s idiotypic VH CDR3 sequence could elicit peptide-specific immune resp onses in a patient with IgA myeloma, Not unlike B-cell lymphoma, the i mmune repertoire of the patient contained T cells capable of mounting proliferative and cytotoxic responses to antigen-presenting cells load ed with the CDR3 peptide. Furthermore, the T cells were also able to s ecrete interferon-gamma upon peptide rechallenge. Antigen recognition by peptide-primed T cells was MHC dependent and could be blocked by an tibodies to both monomorphic MHC class I and class II molecules. These results therefore indicate the presence of T-cell epitopes on the VII CDR3 sequence. In addition, CDR3 peptide-primed T cells were also abl e to mount similar immune responses when rechallenged with the intact IgA idiotypic protein, suggesting that functional T-cell epitopes had been derived from the CDR3 sequence of the idiotypic protein. Our resu lts therefore provide a new perspective to the immunogenicity of the i diotypic protein in myeloma.