Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes
<p>MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8<sup>+</sup> T cells. To understand t...
| প্রধান লেখক: | , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Cell Press
2022
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| _version_ | 1826309311748374528 |
|---|---|
| author | Walters, LC Rozbesky, D Harlos, K Quastel, M Sun, H Springer, S Rambo, RP Mohammed, F Jones, EY McMichael, AJ Gillespie, GM |
| author_facet | Walters, LC Rozbesky, D Harlos, K Quastel, M Sun, H Springer, S Rambo, RP Mohammed, F Jones, EY McMichael, AJ Gillespie, GM |
| author_sort | Walters, LC |
| collection | OXFORD |
| description | <p>MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8<sup>+</sup> T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the α2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting α2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination</p> |
| first_indexed | 2024-03-07T07:33:47Z |
| format | Journal article |
| id | oxford-uuid:b51fc23b-bf51-4801-9294-9fd63b83da30 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:33:47Z |
| publishDate | 2022 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:b51fc23b-bf51-4801-9294-9fd63b83da302023-02-14T15:35:14ZPrimary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b51fc23b-bf51-4801-9294-9fd63b83da30EnglishSymplectic ElementsCell Press2022Walters, LCRozbesky, DHarlos, KQuastel, MSun, HSpringer, SRambo, RPMohammed, FJones, EYMcMichael, AJGillespie, GM<p>MHC-E regulates NK cells by displaying MHC class Ia signal peptides (VL9) to NKG2A:CD94 receptors. MHC-E can also present sequence-diverse, lower-affinity, pathogen-derived peptides to T cell receptors (TCRs) on CD8<sup>+</sup> T cells. To understand these affinity differences, human MHC-E (HLA-E)-VL9 versus pathogen-derived peptide structures are compared. Small-angle X-ray scatter (SAXS) measures biophysical parameters in solution, allowing comparison with crystal structures. For HLA-E-VL9, there is concordance between SAXS and crystal parameters. In contrast, HLA-E-bound pathogen-derived peptides produce larger SAXS dimensions that reduce to their crystallographic dimensions only when excess peptide is supplied. Further crystallographic analysis demonstrates three amino acids, exclusive to MHC-E, that not only position VL9 close to the α2 helix, but also allow non-VL9 peptide binding with re-configuration of a key TCR-interacting α2 region. Thus, non-VL9-bound peptides introduce an alternative peptide-binding motif and surface recognition landscape, providing a likely basis for VL9- and non-VL9-HLA-E immune discrimination</p> |
| spellingShingle | Walters, LC Rozbesky, D Harlos, K Quastel, M Sun, H Springer, S Rambo, RP Mohammed, F Jones, EY McMichael, AJ Gillespie, GM Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title | Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title_full | Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title_fullStr | Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title_full_unstemmed | Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title_short | Primary and secondary functions of HLA-E are determined by stability and conformation of the peptide-bound complexes |
| title_sort | primary and secondary functions of hla e are determined by stability and conformation of the peptide bound complexes |
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