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 occurring major-histocompatibility-complex-dependent idiotype (peptide)-specific T cells in multiple myeloma. The fine specificity of idiotype-reactive, interferon-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 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 VH appeared to be an important target for T cells, since the sequence expressed MHC-class-I- as well as MHC-class-II-restricted 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.
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden. jfa@rah.ks.se
J
J
Fagerberg
Q
Q
Yi
D
D
Gigliotti
U
U
Harmenberg
U
U
Rudén
B
B
Persson
A
A
Osterborg
H
H
Mellstedt
D000368:Aged; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics; D001483:Base Sequence; D000939:Epitopes / Q000235:genetics; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008285:Major Histocompatibility Complex; D008297:Male; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains