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

• Verfasst von: Lotz, Carina [VerfasserIn]
• Verfasst von: Mutallib, Sarah Abdel [VerfasserIn]
• Verfasst von: Oehlrich, Nicole [VerfasserIn]
• Verfasst von: Liewer, Ulrike [VerfasserIn]
• Verfasst von: Ferreira, Edite Antunes [VerfasserIn]
• Verfasst von: Moos, Marion [VerfasserIn]
• Verfasst von: Hundemer, Michael [VerfasserIn]
• Verfasst von: Schneider, Sandra [VerfasserIn]
• Verfasst von: Strand, Susanne [VerfasserIn]
• Verfasst von: Huber, Christoph [VerfasserIn]
• Verfasst von: Goldschmidt, Hartmut [VerfasserIn]
• Verfasst von: Theobald, Matthias [VerfasserIn]
• Titel: Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL
• Verf.angabe: 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
• E-Jahr: 2005
• Jahr: [July 15, 2005]
• Umfang: 9 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 25.02.2022
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2005
• Band/Heft Quelle: 175(2005), 2 vom: Juli, Seite 1301-1309
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.175.2.1301
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 179388871X

Abstract

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.