Structural and regulatory diversity shape HLA-C protein expression levels
Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional cont...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Published: |
Springer Nature
2017
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| _version_ | 1797087423542329344 |
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| author | Kaur, G Gras, S Mobbs, J Vivian, J Cortes, A Barber, T Kuttikkatte, S Jensen, L Attfield, K Dendrou, C Carrington, M McVean, G Purcell, A Rossjohn, J Fugger, L |
| author_facet | Kaur, G Gras, S Mobbs, J Vivian, J Cortes, A Barber, T Kuttikkatte, S Jensen, L Attfield, K Dendrou, C Carrington, M McVean, G Purcell, A Rossjohn, J Fugger, L |
| author_sort | Kaur, G |
| collection | OXFORD |
| description | Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analyses, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression. |
| first_indexed | 2024-03-07T02:35:31Z |
| format | Journal article |
| id | oxford-uuid:a8a507e2-2750-4ca8-8fc9-fc9c96fc82a7 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:35:31Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:a8a507e2-2750-4ca8-8fc9-fc9c96fc82a72022-03-27T03:03:08ZStructural and regulatory diversity shape HLA-C protein expression levelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a8a507e2-2750-4ca8-8fc9-fc9c96fc82a7Symplectic Elements at OxfordSpringer Nature2017Kaur, GGras, SMobbs, JVivian, JCortes, ABarber, TKuttikkatte, SJensen, LAttfield, KDendrou, CCarrington, MMcVean, GPurcell, ARossjohn, JFugger, LExpression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analyses, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression. |
| spellingShingle | Kaur, G Gras, S Mobbs, J Vivian, J Cortes, A Barber, T Kuttikkatte, S Jensen, L Attfield, K Dendrou, C Carrington, M McVean, G Purcell, A Rossjohn, J Fugger, L Structural and regulatory diversity shape HLA-C protein expression levels |
| title | Structural and regulatory diversity shape HLA-C protein expression levels |
| title_full | Structural and regulatory diversity shape HLA-C protein expression levels |
| title_fullStr | Structural and regulatory diversity shape HLA-C protein expression levels |
| title_full_unstemmed | Structural and regulatory diversity shape HLA-C protein expression levels |
| title_short | Structural and regulatory diversity shape HLA-C protein expression levels |
| title_sort | structural and regulatory diversity shape hla c protein expression levels |
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