Inactivation of a defined active site in the mouse 20S proteasome complex enhances major histocompatibility complex class I antigen presentation of a murine cytomegalovirus protein

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1998
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Eggers, Maren
Ruppert, Thomas
Koszinowski, Ulrich
Kloetzel, Peter-M.
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Journal of Experimental Medicine. 1998, 187(10), pp. 1641-1646. ISSN 0022-1007. eISSN 1540-9538. Available under: doi: 10.1084/jem.187.10.1641
Zusammenfassung

Proteasomes generate peptides bound by major histocompatibility complex (MHC) class I molecules. Avoiding proteasome inhibitors, which in most cases do not distinguish between individual active sites within the cell, we used a molecular genetic approach that allowed for the first time the in vivo analysis of defined proteasomal active sites with regard to their significance for antigen processing. Functional elimination of the delta/low molecular weight protein (LMP) 2 sites by substitution with a mutated inactive LMP2 T1A subunit results in reduced cell surface expression of the MHC class I H-2Ld and H-2Dd molecules. Surface levels of H-2Ld and H-2Dd molecules were restored by external loading with peptides. However, as a result of the active site mutation, MHC class I presentation of a 9-mer peptide derived from a protein of murine cytomegalovirus was enhanced about three- to fivefold. Our experiments provide evidence that the delta/LMP2 active site elimination limits the processing and presentation of several peptides, but may be, nonetheless, beneficial for the generation and presentation of others.

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570 Biowissenschaften, Biologie
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proteosome, antigen processing, mutation, active site, low molecular weight protein 2 T1A
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ISO 690SCHMIDTKE, Gunter, Maren EGGERS, Thomas RUPPERT, Marcus GRÖTTRUP, Ulrich KOSZINOWSKI, Peter-M. KLOETZEL, 1998. Inactivation of a defined active site in the mouse 20S proteasome complex enhances major histocompatibility complex class I antigen presentation of a murine cytomegalovirus protein. In: Journal of Experimental Medicine. 1998, 187(10), pp. 1641-1646. ISSN 0022-1007. eISSN 1540-9538. Available under: doi: 10.1084/jem.187.10.1641
BibTex
@article{Schmidtke1998Inact-22242,
  year={1998},
  doi={10.1084/jem.187.10.1641},
  title={Inactivation of a defined active site in the mouse 20S proteasome complex enhances major histocompatibility complex class I antigen presentation of a murine cytomegalovirus protein},
  number={10},
  volume={187},
  issn={0022-1007},
  journal={Journal of Experimental Medicine},
  pages={1641--1646},
  author={Schmidtke, Gunter and Eggers, Maren and Ruppert, Thomas and Gröttrup, Marcus and Koszinowski, Ulrich and Kloetzel, Peter-M.}
}
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