The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation
IntroductionThe presentation of pathogen-derived antigens on major histocompatibility complex (MHC) class I is crucial for the antiviral immune response. Degradation of intracellular pathogen-derived proteins by the 26S proteasome generates peptides that can be loaded on MHC-I molecules and presente...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636951/full |
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| author | Natalie Pach Natalie Pach Sarah Ochs Jinjing Cao Julia Ottlinger Annette Aichem Michael Basler Michael Basler |
| author_facet | Natalie Pach Natalie Pach Sarah Ochs Jinjing Cao Julia Ottlinger Annette Aichem Michael Basler Michael Basler |
| author_sort | Natalie Pach |
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| description | IntroductionThe presentation of pathogen-derived antigens on major histocompatibility complex (MHC) class I is crucial for the antiviral immune response. Degradation of intracellular pathogen-derived proteins by the 26S proteasome generates peptides that can be loaded on MHC-I molecules and presented to cytotoxic T cells. The cytokine-inducible ubiquitin-like modifier (ULM) HLA-F adjacent transcript 10 (FAT10) is encoded in the MHC locus and targets its substrates for proteasomal degradation. Therefore, it acts as an alternative signal for protein degradation, indicating a role in generating the peptide pool for MHC-I presentation. In this study, we aimed to elucidate the role of FAT10 in MHC class I presentation. MethodsUsing different human and mouse cell lines deficient for FAT10, the effect of FAT10 on MHC-I surface expression and recovery was studied. For the evaluation of antigen presentation of viral and endogenous epitopes, T cell hybridoma assays and flow cytometry analysis were used.ResultsIn our study, using model antigens and FAT10-deficient cells, we found that the absence of FAT10 does not affect the abundance of MHC-I molecules or the generation of endogenous and virus-derived MHC-I epitopes. Furthermore, we demonstrated that the cytotoxic T cell response to different viruses remains unchanged in FAT10-deficient mice compared to wild-type mice.DiscussionIn summary, our findings indicate that the lack of FAT10 does not impact antigen presentation or the cytotoxic T-cell response across a number of different MHC-I-restricted peptides. Hence, we conclude that the contribution of FAT10 to MHC-I antigen presentation has previously been overestimated. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-08-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-ecc8f5a2d8a34f75a60f7b06393986452025-08-20T03:32:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16369511636951The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentationNatalie Pach0Natalie Pach1Sarah Ochs2Jinjing Cao3Julia Ottlinger4Annette Aichem5Michael Basler6Michael Basler7Institute of Cell Biology and Immunology Thurgau (BITG) at the University of Konstanz, Kreuzlingen, SwitzerlandDivision of Immunology, Department of Biology, University of Konstanz, Konstanz, GermanyDivision of Immunology, Department of Biology, University of Konstanz, Konstanz, GermanyDivision of Immunology, Department of Biology, University of Konstanz, Konstanz, GermanyInstitute of Cell Biology and Immunology Thurgau (BITG) at the University of Konstanz, Kreuzlingen, SwitzerlandInstitute of Cell Biology and Immunology Thurgau (BITG) at the University of Konstanz, Kreuzlingen, SwitzerlandInstitute of Cell Biology and Immunology Thurgau (BITG) at the University of Konstanz, Kreuzlingen, SwitzerlandDivision of Immunology, Department of Biology, University of Konstanz, Konstanz, GermanyIntroductionThe presentation of pathogen-derived antigens on major histocompatibility complex (MHC) class I is crucial for the antiviral immune response. Degradation of intracellular pathogen-derived proteins by the 26S proteasome generates peptides that can be loaded on MHC-I molecules and presented to cytotoxic T cells. The cytokine-inducible ubiquitin-like modifier (ULM) HLA-F adjacent transcript 10 (FAT10) is encoded in the MHC locus and targets its substrates for proteasomal degradation. Therefore, it acts as an alternative signal for protein degradation, indicating a role in generating the peptide pool for MHC-I presentation. In this study, we aimed to elucidate the role of FAT10 in MHC class I presentation. MethodsUsing different human and mouse cell lines deficient for FAT10, the effect of FAT10 on MHC-I surface expression and recovery was studied. For the evaluation of antigen presentation of viral and endogenous epitopes, T cell hybridoma assays and flow cytometry analysis were used.ResultsIn our study, using model antigens and FAT10-deficient cells, we found that the absence of FAT10 does not affect the abundance of MHC-I molecules or the generation of endogenous and virus-derived MHC-I epitopes. Furthermore, we demonstrated that the cytotoxic T cell response to different viruses remains unchanged in FAT10-deficient mice compared to wild-type mice.DiscussionIn summary, our findings indicate that the lack of FAT10 does not impact antigen presentation or the cytotoxic T-cell response across a number of different MHC-I-restricted peptides. Hence, we conclude that the contribution of FAT10 to MHC-I antigen presentation has previously been overestimated.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636951/fullFAT10UBDproteasomeMHC-Iantigen processingantigen presentation |
| spellingShingle | Natalie Pach Natalie Pach Sarah Ochs Jinjing Cao Julia Ottlinger Annette Aichem Michael Basler Michael Basler The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation Frontiers in Immunology FAT10 UBD proteasome MHC-I antigen processing antigen presentation |
| title | The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation |
| title_full | The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation |
| title_fullStr | The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation |
| title_full_unstemmed | The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation |
| title_short | The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation |
| title_sort | ubiquitin like modifier fat10 is not essential for mhc i antigen presentation |
| topic | FAT10 UBD proteasome MHC-I antigen processing antigen presentation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636951/full |
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