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...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
[July 15, 2005]
|
| In: |
The journal of immunology
Year: 2005, Volume: 175, Issue: 2, Pages: 1301-1309 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.175.2.1301 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.175.2.1301 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/175/2/1301 
|
| Author Notes: | 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 |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 25.02.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.175.2.1301 |