T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma

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 occurrin g major-histocompatibility-complex-dependent idiotype (peptide)specific T c ells in multiple myeloma, The fine specificity of idiotype-reactive, interf eron-gamma-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 region s (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 o f the light chain (V-L) induced a specific T-cell response. The idiotype am ino-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-clas s-II-restricted epitopes. The study provides further support for the existe nce of MHC-restricted idiotype-specific T cells, which may target immunogen ic CDR peptides in multiple myeloma. Such T cells could be an important par t of the specific anti-tumor immune responses induced in idiotype vaccinati on protocols. Int. J. Cancer 80:671-680, 1999. (C) 1999 Wiley-Liss, Inc.