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The Significant Role of PA28αβ in CD8+ T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands

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2024

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Deutsche Forschungsgemeinschaft (DFG): GR 1517/25-1

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International Journal of Molecular Sciences. MDPI. 2024, 25(11), 5649. ISSN 1661-6596. eISSN 1422-0067. Verfügbar unter: doi: 10.3390/ijms25115649

Zusammenfassung

The proteasome generates the majority of peptides presented on MHC class I molecules. The cleavage pattern of the proteasome has been shown to be changed via the proteasome activator (PA)28 alpha beta (PA28αβ). In particular, several immunogenic peptides have been reported to be PA28αβ-dependent. In contrast, we did not observe a major impact of PA28αβ on the generation of different major histocompatibility complex (MHC) classI ligands. PA28αβ-knockout mice infected with the lymphocytic choriomeningitis virus (LCMV) or vaccinia virus showed a normal cluster of differentiation (CD) 8 response and viral clearance. However, we observed that the adoptive transfer of wild-type cells into PA28αβ-knockout mice led to graft rejection, but not vice versa. Depletion experiments showed that the observed rejection was mediated by CD8+ cytotoxic T cells. These data indicate that PA28αβ might be involved in the development of the CD8+ T cell repertoire in the thymus. Taken together, our data suggest that PA28αβ is a crucial factor determining T cell selection and, therefore, impacts graft acceptance.

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

proteasome, PA28αβ, CD8 T cell response, adoptive cell transfer, rejection, antigen processing, antigen presentation

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ISO 690INHOLZ, Katharina, Ulrika BADER, Sarah MUNDT, Michael BASLER, 2024. The Significant Role of PA28αβ in CD8+ T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands. In: International Journal of Molecular Sciences. MDPI. 2024, 25(11), 5649. ISSN 1661-6596. eISSN 1422-0067. Verfügbar unter: doi: 10.3390/ijms25115649
BibTex
@article{Inholz2024Signi-70273,
  year={2024},
  doi={10.3390/ijms25115649},
  title={The Significant Role of PA28αβ in CD8<sup>+</sup> T Cell-Mediated Graft Rejection Contrasts with Its Negligible Impact on the Generation of MHC-I Ligands},
  number={11},
  volume={25},
  issn={1661-6596},
  journal={International Journal of Molecular Sciences},
  author={Inholz, Katharina and Bader, Ulrika and Mundt, Sarah and Basler, Michael},
  note={Article Number: 5649}
}
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