A natural tapasin isoform lacking exon 3 modifies peptide loading complex function

Nele Beutler, Sebastian Hauka, Alexandra Niepel, Daniel Johannes Kowalewski, Julia Uhlmann, Esther Ghanem, Steffen Erkelenz, Constanze Wiek, Helmut Hanenberg, Heiner Schaal, Stefan Stevanović, Sebastian Springer, Frank Momburg, Hartmut Hengel, Anne Halenius

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

To assure efficient MHC class I (MHC-I) peptide loading, the peptide loading complex (PLC) recruits the peptide-receptive form of MHC-I, and in this process, tapasin (tpn) connects MHC-I with the peptide transporter TAP and forms a stable disulfide bond with ERp57. Here, we describe an alternatively spliced tpn transcript lacking exon 3, observed in cells infected with human cytomegalovirus. Recognition of exon 3 was regulated via G-runs, suggesting that members of the hnRNP (heterogeneous nuclear ribonucleoprotein)-family regulate expression of the ΔExon3 variant of tpn. Exon 3 includes Cys-95, which is responsible for the disulfide bond formation with ERp57 and, consequently, interaction of the ΔExon3 variant with ERp57 was strongly impaired. Although the ΔExon3 variant specifically stabilized TAP expression but not MHC-I in tpn-deficient cells, in tpn-proficient cells, the ΔExon3 tpn reduced cell surface expression of the tpn-dependent HLA-B*44:02 allele; the stability of the tpn-independent HLA-B*44:05 was not affected. Most importantly, detailed analysis of the PLC revealed a simultaneous binding of the ΔExon3 variant and tpn to TAP, suggesting modification of PLC functions. Indeed, an altered MHC-I ligandome was observed in HeLa cells overexpressing the ΔExon3 variant, highlighting the potential of the alternatively spliced tpn variant to impact CD8+ T-cell responses.

Original languageEnglish
Pages (from-to)1459-1469
Number of pages11
JournalEuropean Journal of Immunology
Volume43
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Exons
Protein Isoforms
Peptides
HLA-B Antigens
Disulfides
tapasin
Heterogeneous-Nuclear Ribonucleoproteins
Cytomegalovirus
Nuclear Family
HeLa Cells
Alleles
T-Lymphocytes

Keywords

  • MHC class I peptide loading
  • PLC
  • TAP
  • Tapasin

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Beutler, N., Hauka, S., Niepel, A., Kowalewski, D. J., Uhlmann, J., Ghanem, E., ... Halenius, A. (2013). A natural tapasin isoform lacking exon 3 modifies peptide loading complex function. European Journal of Immunology, 43(6), 1459-1469. https://doi.org/10.1002/eji.201242725

A natural tapasin isoform lacking exon 3 modifies peptide loading complex function. / Beutler, Nele; Hauka, Sebastian; Niepel, Alexandra; Kowalewski, Daniel Johannes; Uhlmann, Julia; Ghanem, Esther; Erkelenz, Steffen; Wiek, Constanze; Hanenberg, Helmut; Schaal, Heiner; Stevanović, Stefan; Springer, Sebastian; Momburg, Frank; Hengel, Hartmut; Halenius, Anne.

In: European Journal of Immunology, Vol. 43, No. 6, 06.2013, p. 1459-1469.

Research output: Contribution to journalArticle

Beutler, N, Hauka, S, Niepel, A, Kowalewski, DJ, Uhlmann, J, Ghanem, E, Erkelenz, S, Wiek, C, Hanenberg, H, Schaal, H, Stevanović, S, Springer, S, Momburg, F, Hengel, H & Halenius, A 2013, 'A natural tapasin isoform lacking exon 3 modifies peptide loading complex function', European Journal of Immunology, vol. 43, no. 6, pp. 1459-1469. https://doi.org/10.1002/eji.201242725
Beutler N, Hauka S, Niepel A, Kowalewski DJ, Uhlmann J, Ghanem E et al. A natural tapasin isoform lacking exon 3 modifies peptide loading complex function. European Journal of Immunology. 2013 Jun;43(6):1459-1469. https://doi.org/10.1002/eji.201242725
Beutler, Nele ; Hauka, Sebastian ; Niepel, Alexandra ; Kowalewski, Daniel Johannes ; Uhlmann, Julia ; Ghanem, Esther ; Erkelenz, Steffen ; Wiek, Constanze ; Hanenberg, Helmut ; Schaal, Heiner ; Stevanović, Stefan ; Springer, Sebastian ; Momburg, Frank ; Hengel, Hartmut ; Halenius, Anne. / A natural tapasin isoform lacking exon 3 modifies peptide loading complex function. In: European Journal of Immunology. 2013 ; Vol. 43, No. 6. pp. 1459-1469.
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AU - Erkelenz, Steffen

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AU - Hanenberg, Helmut

AU - Schaal, Heiner

AU - Stevanović, Stefan

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