Intracellular trafficking of HLA-E and its regulation
Interest in MHC-E–restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)–restricted CD8+ T cell response requir...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Rockefeller University Press
2023
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| _version_ | 1797111015320584192 |
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| author | He, W Gea-Mallorqui, E Colin-York, H Fritzsche, M Gillespie, GM Brackenridge, S Borrow, P McMichael, AJ |
| author_facet | He, W Gea-Mallorqui, E Colin-York, H Fritzsche, M Gillespie, GM Brackenridge, S Borrow, P McMichael, AJ |
| author_sort | He, W |
| collection | OXFORD |
| description | Interest in MHC-E–restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)–restricted CD8+ T cell response requires an understanding of the pathway(s) of HLA-E transport and antigen presentation, which have not been clearly defined previously. We show here that, unlike classical HLA class I, which rapidly exits the endoplasmic reticulum (ER) after synthesis, HLA-E is largely retained because of a limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and is rapidly internalized. The cytoplasmic tail plays a crucial role in facilitating HLA-E internalization, which results in its enrichment in late and recycling endosomes. Our data reveal distinctive transport patterns and delicate regulatory mechanisms of HLA-E, which help to explain its unusual immunological functions. |
| first_indexed | 2024-03-07T08:04:19Z |
| format | Journal article |
| id | oxford-uuid:e2347a97-86b2-4149-ba70-7170ef7551ba |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:04:19Z |
| publishDate | 2023 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:e2347a97-86b2-4149-ba70-7170ef7551ba2023-10-13T08:59:48ZIntracellular trafficking of HLA-E and its regulationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e2347a97-86b2-4149-ba70-7170ef7551baEnglishSymplectic ElementsRockefeller University Press2023He, WGea-Mallorqui, EColin-York, HFritzsche, MGillespie, GMBrackenridge, SBorrow, PMcMichael, AJInterest in MHC-E–restricted CD8+ T cell responses has been aroused by the discovery of their efficacy in controlling simian immunodeficiency virus (SIV) infection in a vaccine model. The development of vaccines and immunotherapies utilizing human MHC-E (HLA-E)–restricted CD8+ T cell response requires an understanding of the pathway(s) of HLA-E transport and antigen presentation, which have not been clearly defined previously. We show here that, unlike classical HLA class I, which rapidly exits the endoplasmic reticulum (ER) after synthesis, HLA-E is largely retained because of a limited supply of high-affinity peptides, with further fine-tuning by its cytoplasmic tail. Once at the cell surface, HLA-E is unstable and is rapidly internalized. The cytoplasmic tail plays a crucial role in facilitating HLA-E internalization, which results in its enrichment in late and recycling endosomes. Our data reveal distinctive transport patterns and delicate regulatory mechanisms of HLA-E, which help to explain its unusual immunological functions. |
| spellingShingle | He, W Gea-Mallorqui, E Colin-York, H Fritzsche, M Gillespie, GM Brackenridge, S Borrow, P McMichael, AJ Intracellular trafficking of HLA-E and its regulation |
| title | Intracellular trafficking of HLA-E and its regulation |
| title_full | Intracellular trafficking of HLA-E and its regulation |
| title_fullStr | Intracellular trafficking of HLA-E and its regulation |
| title_full_unstemmed | Intracellular trafficking of HLA-E and its regulation |
| title_short | Intracellular trafficking of HLA-E and its regulation |
| title_sort | intracellular trafficking of hla e and its regulation |
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