Tapasin facilitation of MHC-I separates closely related allomorphs, is strongly influenced by peptide length and depends on stability

Linda Geironson Ulfsson, Camilla Thuring, Mikkel Harndahl, M. Rasmussen, Søren Buus, Gustav Røder, Kajsa Paulsson

Research output: Contribution to conferenceAbstractpeer-review


Only a small fraction of the peptides inside a cell are eventually presented by HLA-I on the cell surface. The presented peptides have HLA-I allomorph-specific motifs and length restrictions. Tapasin influences HLA-I antigen presentation both qualitatively and quantitatively to different degrees depending on both peptide sequence and HLA-I allomorph. The tapasin-dependence in cellular context has been shown to correspond to the facilitation of peptide- HLA-I complex formation by the first 87 amino acids of tapasin (Tpn1- 87) (i.e., tapasin-facilitation = Bmax Tpn1-87/Bmax Ctrl) in a biochemical assay. Both peptide length and tapasin-facilitation are important for HLA-I antigen presentation and we here set out to study if these two parameters relate to each other. We used a luminescent oxygen channeling assay and seven different peptide libraries (X7- X13) to study 16 HLA-A and -B allomorphs and the results show a broad spectrum of tapasin-facilitation of HLA-I allomorphs and that HLA-A allomorphs were generally less restricted than -B allomorphs
to peptides of the classical lengths of 8-10 amino acids. Since both stability and tapasin-facilitation have been suggested as discriminators of immunogenic peptides we used a scintillation proximity based assay to study the stability of peptide-HLA-I complexes formed with peptides of different lengths. The results demonstrate an inverse correlation between tapasin-facilitation and stability valid for different peptide mixes of specific lengths but also on the level of HLA-I allomorphs, suggesting that molecules of poor stability are either not in a conformation that allows tapasin to interact or have a conformation where association has no effect.
Original languageEnglish
Number of pages1
Publication statusPublished - 2013 Aug
EventICI 2013: International congress of immunology Milan, Immunitas vis naturae - Milan, Italy
Duration: 2013 Aug 222013 Aug 27


ConferenceICI 2013
Abbreviated titleICI 2013

Subject classification (UKÄ)

  • Cell and Molecular Biology

Free keywords

  • tapasin
  • peptide
  • HLA-I
  • MHC-I
  • antigen presentation


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