Immunogenicity and cross-reactivity with idiotypic IgA of VH CDR3 peptide in multiple myeloma.
Multiple myeloma idiotypic protein is clone-specific and therefore represents an ideal tumour antigen for immune targeting. In this study we determined whether a synthetic peptide corresponding to the autologous idiotypic VH CDR3 sequence could elicit peptide-specific immune responses in a patient with IgA myeloma. Not unlike B-cell lymphoma, the immune repertoire of the patient contained T cells capable of mounting proliferative and cytotoxic responses to antigen-presenting cells loaded with the CDR3 peptide. Furthermore, the T cells were also able to secrete interferon-gamma upon peptide rechallenge. Antigen recognition by peptide-primed T cells was MHC dependent and could be blocked by antibodies to both monomorphic MHC class I and class II molecules. These results therefore indicate the presence of T-cell epitopes on the VH CDR3 sequence. In addition, CDR3 peptide-primed T cells were also able 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 results therefore provide a new perspective to the immunogenicity of the idiotypic protein in myeloma.
Wen
Y J
YJ
Department of Haematology, University of Wales College of Medicine, Cardiff.
Ling
M
M
Lim
S H
SH
D002455:Cell Division; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D009101:Multiple Myeloma / Q000276:immunology*; D009194:Myeloma Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000939:Epitopes; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins; D007371:Interferon-gamma