T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma
✍ Scribed by Jan Fagerberg; Qing Yi; Dulceaydee Gigliotti; Ulrika Harmenberg; Ulla Rudén; Bengt Persson; Anders Österborg; Håkan Mellstedt
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 196 KB
- Volume
- 80
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The idiotypic structures of the myeloma protein might be regarded as tumor-specific antigens. The present study was designed to map T-cell epitopes of the idiotypic myeloma protein to prove the existence of naturally occurring majorhistocompatibility-complex-dependent idiotype (peptide)specific T cells in multiple myeloma. The fine specificity of idiotype-reactive, interferon-␥-producing blood T cells of a patient with multiple myeloma stage I was characterized by identification of idiotype (heavy and light chains)-derived MHC-restricted T-cell epitopes. T cells specifically reacting with peptides corresponding to each of the 3 complementarity-determining regions (CDRs) of the heavy-chain variable part (V H ) of the autologous idiotype were found. In contrast, none of the peptides corresponding to the 3 CDRs of the light chain (V L ) induced a specific T-cell response. The idiotype amino-acid sequence corresponding to the junction of the V H , diversity (D), and joining (J) gene segments of the V H appeared to be an important target for T cells, since the sequence expressed MHC-class-I-as well as MHC-class-IIrestricted epitopes. The study provides further support for the existence of MHC-restricted idiotype-specific T cells, which may target immunogenic CDR peptides in multiple myeloma. Such T cells could be an important part of the specific anti-tumor immune responses induced in idiotype vaccination protocols. Int.