The ubiquitin-like modifier FAT10 is not essential for MHC-I antigen presentation

Michael Basler^1,2*Natalie Pach^2,3Sarah Ochs³Jinjing Cao³Julia # Ottlinger²Annette Aichem²

• ¹Department of Biology, Mathematical Natural Science Section, University of Konstanz, Konstanz, Germany
• ²Institut fur Zellulare Biologie und Immunologie Thurgau an der Universitat Konstanz, Kreuzlingen, Switzerland
• ³Universitat Konstanz Fachbereich Biologie, Konstanz, Germany

The 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 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. In 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.