| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Kempkes, Bettina God, Jason M. Bornkamm, Georg W. Haque, Azizul Hossain, Azim Stuart, Robert K. Cameron, Christine Amria, Shereen Blum, Janice S. Figueroa, Janette |
| Description |
Author Affiliation: God JM ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425); Cameron C ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425); Figueroa J ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425); Amria S ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425); Hossain A ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425); Kempkes B ( Department of Gene Vectors, German Research Center for Environmental Health, 81377 Munich, Germany); Bornkamm GW ( Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, 81377 Munich, Germany); Stuart RK ( Department of Hematology and Oncology, Medical University of South Carolina, Charleston, SC 29425); Blum JS ( Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.); Haque A ( Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425) |
| Abstract |
Elevated levels of the transcription factor c-myc are strongly associated with various cancers, and in particular B cell lymphomas. Although many of c-MYC's functions have been elucidated, its effect on the presentation of Ag through the HLA class II pathway has not been reported previously. This is an issue of considerable importance, given the low immunogenicity of many c-MYC-positive tumors. We report in this paper that increased c-MYC expression has a negative effect on the ability of B cell lymphomas to functionally present Ags/peptides to CD4(+) T cells. This defect was associated with alterations in the expression of distinct cofactors as well as interactions of antigenic peptides with class II molecules required for the presentation of class II-peptide complexes and T cell engagement. Using early passage Burkitt's lymphoma (BL) tumors and transformed cells, we show that compared with B lymphoblasts, BL cells express decreased levels of the class II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47-kDa enolase-like protein. Functional Ag presentation was partially restored in BL cells treated with a c-MYC inhibitor, demonstrating the impact of this oncogene on Ag recognition. This restoration of HLA class II-mediated Ag presentation in early passage BL tumors/cells was linked to enhanced HLA-DM expression and a concurrent decrease in HLA-DO in BL cells. Taken together, these results reveal c-MYC exerts suppressive effects at several critical checkpoints in Ag presentation, which contribute to the immunoevasive properties of BL tumors. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| DOI |
10.4049/jimmunol.1402382 |
| Journal |
The Journal of Immunology |
| Issue Number |
4 |
| Volume Number |
194 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2015-02-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Antigen Presentation Immunology Histocompatibility Antigens Class Ii Lymphoma, B-cell Proto-oncogene Proteins C-myc Tumor Escape Blotting, Western Flow Cytometry Mass Spectrometry Spectrometry, Mass, Matrix-assisted Laser Desorption-ionization Tumor Cells, Cultured Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
