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Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL

Growing evidence indicates that multiple myeloma (MM) and other malignancies are susceptible to CTL-based immune interventions. We studied whether transcription factors inherently involved in the terminal differentiation of mature B lymphocytes into malignant and nonmalignant plasma cells provide MM...

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Hauptverfasser: Lotz, Carina (VerfasserIn) , Mutallib, Sarah Abdel (VerfasserIn) , Oehlrich, Nicole (VerfasserIn) , Liewer, Ulrike (VerfasserIn) , Ferreira, Edite Antunes (VerfasserIn) , Moos, Marion (VerfasserIn) , Hundemer, Michael (VerfasserIn) , Schneider, Sandra (VerfasserIn) , Strand, Susanne (VerfasserIn) , Huber, Christoph (VerfasserIn) , Goldschmidt, Hartmut (VerfasserIn) , Theobald, Matthias (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: [July 15, 2005]
In: The journal of immunology
Year: 2005, Jahrgang: 175, Heft: 2, Pages: 1301-1309
ISSN:1550-6606
DOI:10.4049/jimmunol.175.2.1301
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.175.2.1301
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/175/2/1301
Volltext
Verfasserangaben:Carina Lotz, Sarah Abdel Mutallib, Nicole Oehlrich, Ulrike Liewer, Edite Antunes Ferreira, Marion Moos, Michael Hundemer, Sandra Schneider, Susanne Strand, Christoph Huber, Hartmut Goldschmidt, and Matthias Theobald
Beschreibung
Zusammenfassung:Growing evidence indicates that multiple myeloma (MM) and other malignancies are susceptible to CTL-based immune interventions. We studied whether transcription factors inherently involved in the terminal differentiation of mature B lymphocytes into malignant and nonmalignant plasma cells provide MM-associated CTL epitopes. HLA-A*0201 (A2.1) transgenic mice were used to identify A2.1-presented peptide Ag derived from the plasma cell-associated transcriptional regulators, positive regulatory domain I-binding factor 1 (PRDI-BF1) and X box-binding protein 1 (XBP-1). A2.1-restricted CTL specific for PRDI-BF1 and XBP-1 epitopes efficiently killed a variety of MM targets. PRDI-BF1- and XBP-1-reactive CTL were able to recognize primary MM cells from A2.1+ patients. Consistent with the expression pattern of both transcription factors beyond malignant and nonmalignant plasma cells, PRDI-BF1- and XBP-1-specific CTL activity was not entirely limited to MM targets, but was also associated with lysis of certain other malignancies and, in defined instances, with low-to-intermediate level recognition of a few types of normal cells. Our results also indicate that the A2.1-restricted, PRDI-BF1- and XBP-1-specific human CD8+ T cell repertoire is affected by partial self tolerance and may thus require the transfer of high-affinity TCR to break tolerance. We conclude that transcription factors governing terminal cellular differentiation may provide MM- and tumor-associated CTL epitopes.
Beschreibung:Gesehen am 25.02.2022
Beschreibung:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.175.2.1301

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