Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth
Summary: Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) mole...
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015018 |
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| author | Joanna Bandola-Simon Yoshinaga Ito Kai W. Wucherpfennig Paul A. Roche |
| author_facet | Joanna Bandola-Simon Yoshinaga Ito Kai W. Wucherpfennig Paul A. Roche |
| author_sort | Joanna Bandola-Simon |
| collection | DOAJ |
| description | Summary: Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides. DCs in mice expressing a mutation in the invariant chain sequence that results in enhanced MHC-II-CLIP accumulation are poor stimulators of CD4 T cells and have diminished anti-tumor responses. Our data reveal a previously unknown mechanism of immune evasion in which enhanced expression of MHC-II-CLIP complexes on tumor-draining lymph node DCs limits MHC-II availability for tumor peptides. |
| format | Article |
| id | doaj-art-5b3d5cc680da42d1b81317af8f7040e5 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-5b3d5cc680da42d1b81317af8f7040e52025-01-04T04:56:17ZengElsevierCell Reports2211-12472025-01-01441115150Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growthJoanna Bandola-Simon0Yoshinaga Ito1Kai W. Wucherpfennig2Paul A. Roche3Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAInstitute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, JapanDepartment of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA 02115, USAExperimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding authorSummary: Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides. DCs in mice expressing a mutation in the invariant chain sequence that results in enhanced MHC-II-CLIP accumulation are poor stimulators of CD4 T cells and have diminished anti-tumor responses. Our data reveal a previously unknown mechanism of immune evasion in which enhanced expression of MHC-II-CLIP complexes on tumor-draining lymph node DCs limits MHC-II availability for tumor peptides.http://www.sciencedirect.com/science/article/pii/S2211124724015018CP: ImmunologyCP: Cancer |
| spellingShingle | Joanna Bandola-Simon Yoshinaga Ito Kai W. Wucherpfennig Paul A. Roche Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth Cell Reports CP: Immunology CP: Cancer |
| title | Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth |
| title_full | Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth |
| title_fullStr | Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth |
| title_full_unstemmed | Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth |
| title_short | Defective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth |
| title_sort | defective removal of invariant chain peptides from mhc class ii suppresses tumor antigen presentation and promotes tumor growth |
| topic | CP: Immunology CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015018 |
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