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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636951/full |
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| Summary: | 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. |
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| ISSN: | 1664-3224 |