Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes fromed with natural ligands
Roder, Gustav ; Geironson Ulfsson, Linda LU ; Rasmussen, Michael ; Harndahl Nord, Mikkel ; Buus, Sören and Paulsson, Kajsa M LU
(2011)
In Journal of Biological Chemistry
286(23).
p.20547-20557
- Abstract
- A plethora of peptides are generated intracellularly, and most peptide-human leukocyte antigen (HLA)-I interactions are of a transient, unproductive nature. Without a quality control mechanism, the HLA-I system would be stressed by futile attempts to present peptides not sufficient for the stable peptide-HLA-I complex formation required for long term presentation. Tapasin is thought to be central to this essential quality control, but the underlying mechanisms remain unknown. Here, we report that the N-terminal region of tapasin, Tpn(1-87), assisted folding of peptide-HLA-A*02:01 complexes according to the identity of the peptide. The facilitation was also specific for the identity of the HLA-I heavy chain, where it correlated to... (More)
- A plethora of peptides are generated intracellularly, and most peptide-human leukocyte antigen (HLA)-I interactions are of a transient, unproductive nature. Without a quality control mechanism, the HLA-I system would be stressed by futile attempts to present peptides not sufficient for the stable peptide-HLA-I complex formation required for long term presentation. Tapasin is thought to be central to this essential quality control, but the underlying mechanisms remain unknown. Here, we report that the N-terminal region of tapasin, Tpn(1-87), assisted folding of peptide-HLA-A*02:01 complexes according to the identity of the peptide. The facilitation was also specific for the identity of the HLA-I heavy chain, where it correlated to established tapasin dependence hierarchies. Two large sets of HLA-A*02:01 binding peptides, one extracted from natural HLA-I ligands from the SYFPEITHI database and one consisting of medium to high affinity non-SYFPEITHI ligands, were studied in the context of HLA-A*02:01 binding and stability. We show that the SYFPEITHI peptides induced more stable HLA-A*02:01 molecules than the other ligands, although affinities were similar. Remarkably, Tpn(1-87) could functionally discriminate the selected SYFPEITHI peptides from the other peptide binders with high sensitivity and specificity. We suggest that this HLA-I- and peptide-specific function, together with the functions exerted by the more C-terminal parts of tapasin, are major features of tapasin-mediated HLA-I quality control. These findings are important for understanding the biogenesis of HLA-I molecules, the selection of presented T-cell epitopes, and the identification of immunogenic targets in both basic research and vaccine design. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2438664
- author
- Roder, Gustav
; Geironson Ulfsson, Linda
LU
; Rasmussen, Michael
; Harndahl Nord, Mikkel
; Buus, Sören
and Paulsson, Kajsa M
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Antigen presentation, Antigen processing, Chaperone chaperonin, MHC, Peptides, Tapasin
- in
- Journal of Biological Chemistry
- volume
- 286
- issue
- 23
- pages
- 20547 - 20557
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000291267600041
- scopus:79957972468
- pmid:21518758
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.230151
- language
- English
- LU publication?
- yes
- id
- 5d385238-1b4f-43fb-b8d2-cf65f07d7aeb (old id 2438664)
- date added to LUP
- 2016-04-01 10:09:51
- date last changed
- 2022-01-25 20:25:31
@article{5d385238-1b4f-43fb-b8d2-cf65f07d7aeb,
abstract = {{A plethora of peptides are generated intracellularly, and most peptide-human leukocyte antigen (HLA)-I interactions are of a transient, unproductive nature. Without a quality control mechanism, the HLA-I system would be stressed by futile attempts to present peptides not sufficient for the stable peptide-HLA-I complex formation required for long term presentation. Tapasin is thought to be central to this essential quality control, but the underlying mechanisms remain unknown. Here, we report that the N-terminal region of tapasin, Tpn(1-87), assisted folding of peptide-HLA-A*02:01 complexes according to the identity of the peptide. The facilitation was also specific for the identity of the HLA-I heavy chain, where it correlated to established tapasin dependence hierarchies. Two large sets of HLA-A*02:01 binding peptides, one extracted from natural HLA-I ligands from the SYFPEITHI database and one consisting of medium to high affinity non-SYFPEITHI ligands, were studied in the context of HLA-A*02:01 binding and stability. We show that the SYFPEITHI peptides induced more stable HLA-A*02:01 molecules than the other ligands, although affinities were similar. Remarkably, Tpn(1-87) could functionally discriminate the selected SYFPEITHI peptides from the other peptide binders with high sensitivity and specificity. We suggest that this HLA-I- and peptide-specific function, together with the functions exerted by the more C-terminal parts of tapasin, are major features of tapasin-mediated HLA-I quality control. These findings are important for understanding the biogenesis of HLA-I molecules, the selection of presented T-cell epitopes, and the identification of immunogenic targets in both basic research and vaccine design.}},
author = {{Roder, Gustav and Geironson Ulfsson, Linda and Rasmussen, Michael and Harndahl Nord, Mikkel and Buus, Sören and Paulsson, Kajsa M}},
issn = {{1083-351X}},
keywords = {{Antigen presentation; Antigen processing; Chaperone chaperonin; MHC; Peptides; Tapasin}},
language = {{eng}},
number = {{23}},
pages = {{20547--20557}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes fromed with natural ligands}},
url = {{https://lup.lub.lu.se/search/files/1617183/2438675.pdf}},
doi = {{10.1074/jbc.M111.230151}},
volume = {{286}},
year = {{2011}},
}