HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses
Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be...
| Autori principali: | , , , , , , , , , , , , , , , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
Springer Nature
2023
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| _version_ | 1826311585305460736 |
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| author | Lin, Z Bashirova, AA Viard, M Garner, L Quastel, M Beiersdorfer, M Kasprzak, WK Akdag, M Yuki, Y Ojeda, P Das, S Andresson, T Naranbhai, V Horowitz, A McMichael, AJ Hoelzemer, A Gillespie, GM Garcia-Beltran, WF Carrington, M |
| author_facet | Lin, Z Bashirova, AA Viard, M Garner, L Quastel, M Beiersdorfer, M Kasprzak, WK Akdag, M Yuki, Y Ojeda, P Das, S Andresson, T Naranbhai, V Horowitz, A McMichael, AJ Hoelzemer, A Gillespie, GM Garcia-Beltran, WF Carrington, M |
| author_sort | Lin, Z |
| collection | OXFORD |
| description | Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term ‘functional SPs’. The single functional HLA-B SP, known as HLA-B/−21M, induced high HLA-E expression, but conferred the lowest receptor recognition. Consequently, HLA-B/−21M SP competes with other SPs for providing epitope to HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for reassessment of previous disease models involving HLA-B/−21M. Genetic population data indicate a positive correlation between frequencies of functional SPs in humans and corresponding cytomegalovirus mimics, suggesting a means for viral escape from host responses. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2–HLA-E interactions in disease resistance/susceptibility. |
| first_indexed | 2024-03-07T08:11:56Z |
| format | Journal article |
| id | oxford-uuid:f8bad7a9-9c2e-4664-b4bb-4e8b3d3b0ff9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:11:56Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:f8bad7a9-9c2e-4664-b4bb-4e8b3d3b0ff92023-12-01T09:14:10ZHLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responsesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f8bad7a9-9c2e-4664-b4bb-4e8b3d3b0ff9EnglishSymplectic ElementsSpringer Nature2023Lin, ZBashirova, AAViard, MGarner, LQuastel, MBeiersdorfer, MKasprzak, WKAkdag, MYuki, YOjeda, PDas, SAndresson, TNaranbhai, VHorowitz, AMcMichael, AJHoelzemer, AGillespie, GMGarcia-Beltran, WFCarrington, MHuman leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that among 16 common classical HLA class I SP variants, only 6 can be efficiently processed to generate epitopes that enable CD94/NKG2 engagement, which we term ‘functional SPs’. The single functional HLA-B SP, known as HLA-B/−21M, induced high HLA-E expression, but conferred the lowest receptor recognition. Consequently, HLA-B/−21M SP competes with other SPs for providing epitope to HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for reassessment of previous disease models involving HLA-B/−21M. Genetic population data indicate a positive correlation between frequencies of functional SPs in humans and corresponding cytomegalovirus mimics, suggesting a means for viral escape from host responses. The systematic, quantitative approach described herein will facilitate development of prediction algorithms for accurately measuring the impact of CD94/NKG2–HLA-E interactions in disease resistance/susceptibility. |
| spellingShingle | Lin, Z Bashirova, AA Viard, M Garner, L Quastel, M Beiersdorfer, M Kasprzak, WK Akdag, M Yuki, Y Ojeda, P Das, S Andresson, T Naranbhai, V Horowitz, A McMichael, AJ Hoelzemer, A Gillespie, GM Garcia-Beltran, WF Carrington, M HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title | HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title_full | HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title_fullStr | HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title_full_unstemmed | HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title_short | HLA class I signal peptide polymorphism determines the level of CD94/NKG2–HLA-E-mediated regulation of effector cell responses |
| title_sort | hla class i signal peptide polymorphism determines the level of cd94 nkg2 hla e mediated regulation of effector cell responses |
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