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

Jan Fagerberg, Qing Yi, Dulceaydee Gigliotti, Ulrika Harmenberg, Ulla Rudén, Bengt Persson, Anders Österborg, Håkan Mellstedt

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

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-γ-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-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.

Original languageEnglish (US)
Pages (from-to)671-680
Number of pages10
JournalInternational Journal of Cancer
Volume80
Issue number5
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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