title: T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma.
abstract: The idiotypic structure of the monoclonal immunoglobulin (Ig) in multiple myeloma (MM) might be regarded as a tumor-specific antigen. The present study was designed to identify T-cell epitopes of the variable region of the Ig heavy chain (VH) in MM (n = 5) using bioinformatics and analyze the presence of naturally occurring T cells against idiotype-derived peptides. A large number of human-leukocyte-antigen (HLA)-binding (class I and II) peptides were identified. The frequency of predicted epitopes depended on the database used: 245 in bioinformatics and molecular analysis section (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%, respectively). Most of the predicted peptides were confined to the CDR2-FR3-CDR3 "geographic" region of the Ig-VH region (70%), and significantly fewer peptides were found within the flanking (FR1-CDR1-FR2 and FR4) regions (P <.01). There were 8- to 10-amino acid (aa) long peptides corresponding to the CDRs and fitting to the actual HLA-A/B haplotypes that spontaneously recognized, albeit with a low magnitude, type I T cells (interferon gamma), indicating an ongoing major histocompatibility complex (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- to 20-aa long CDR1-3-derived peptides also spontaneously recognized 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.
authors.affiliation: Department of Hematology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Hansson
authors.forename: Hodjattallah
authors.initials: H
authors.lastname: Rabbani
authors.forename: Jan
authors.initials: J
authors.lastname: Fagerberg
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Håkan
authors.initials: H
authors.lastname: Mellstedt
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides; D007371:Interferon-gamma