Tapasin facilitation of MHC-I separates closely related allomorphs, is strongly influenced by peptide length and depends on stability
(2013) ICI 2013 p.83-83- Abstract
- 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... (More)
- 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
83
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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/878cf28e-024f-414f-b8a3-e816afa4e41a
- author
- Geironson Ulfsson, Linda LU ; Thuring, Camilla LU ; Harndahl, Mikkel ; Rasmussen, M. ; Buus, Søren ; Røder, Gustav and Paulsson, Kajsa LU
- organization
- publishing date
- 2013-08
- type
- Contribution to conference
- publication status
- published
- subject
- keywords
- tapasin, peptide, HLA-I, MHC-I, antigen presentation
- pages
- 1 pages
- conference name
- ICI 2013
- conference location
- Milan, Italy
- conference dates
- 2013-08-22 - 2013-08-27
- language
- English
- LU publication?
- yes
- id
- 878cf28e-024f-414f-b8a3-e816afa4e41a
- alternative location
- http://www.ici2013.org/pdf/uploads/abstracts-book.pdf
- date added to LUP
- 2016-10-28 11:38:58
- date last changed
- 2019-03-08 03:16:04
@misc{878cf28e-024f-414f-b8a3-e816afa4e41a, abstract = {{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<br/>83<br/>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.}}, author = {{Geironson Ulfsson, Linda and Thuring, Camilla and Harndahl, Mikkel and Rasmussen, M. and Buus, Søren and Røder, Gustav and Paulsson, Kajsa}}, keywords = {{tapasin; peptide; HLA-I; MHC-I; antigen presentation}}, language = {{eng}}, pages = {{83--83}}, title = {{Tapasin facilitation of MHC-I separates closely related allomorphs, is strongly influenced by peptide length and depends on stability}}, url = {{http://www.ici2013.org/pdf/uploads/abstracts-book.pdf}}, year = {{2013}}, }