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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-04-1250.

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2002-04-1250v1
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Submitted April 29, 2002
Accepted January 23, 2003

T-cell epitopes within the complementarity-determining and framework regions of the tumor derived immunoglobulin heavy chain in multiple myeloma

Lotta Hansson, Hodjattallah Rabbani, Jan Fagerberg, Anders Osterborg*, and Hakan Mellstedt

Department of Hematology, Karolinska Hospital, Stockholm, Sweden
Department of Oncology (Radiumhemmet) and CancerCentreKarolinska, Karolinska Hospital, Stockholm, Sweden

* Corresponding author; email: anders.osterborg {at}ks.se.

The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain in MM (n=5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype derived peptides. A large number of HLA-binding (class I and II) peptides were identified. The frequency of predicted epitopes was depended on the database used: 245 in BIMAS and 601 in SYFPEITHI. Most of the peptides displayed a binding-half-life or score in the low or intermediate affinity range. The majority of the predicted peptides were complementarity-determining region (CDR) rather than framework region (FR) derived (52-60% vs. 40-48%). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 geographicalregion of the Ig-VH region (70%) and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (p=<0.01). Eight to ten amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplo-types recognized spontaneously albeit with a low magnitude type I T cells (IFN-{gamma}) indicating an ongoing MHC class I restricted T-cell response. Most of those peptides had a low binding half-life (BIMAS) and a low/intermediate score (SYFPEITHI). Furthermore, 15-20 aa long CDR 1-3 derived peptides recognized also spontaneously type I T cells indicating the presence of MHC class II restricted T cells as well. This study demonstrates that a large number of HLA-binding idiotypic peptides can be identified in patients with MM. Such peptides may spontaneously induce a type I MHC class I as well as class II restricted memory T cell response.


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