Journal article
Structural and regulatory diversity shape HLA-C protein expression levels
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.8MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms15924
Authors
+ Oak Foundation
More from this funder
- Funding agency for:
- Fugger, L
- Grant:
- 100308/Z/12/Z
- 106130/Z/14/Z
+ Wellcome Trust
More from this funder
- Funding agency for:
- Fugger, L
- Grant:
- 100308/Z/12/Z
- 106130/Z/14/Z
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 8
- Article number:
- 15924
- Publication date:
- 2017-06-26
- Acceptance date:
- 2017-05-12
- DOI:
- ISSN:
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2041-1723
- Pubs id:
-
pubs:698065
- UUID:
-
uuid:a8a507e2-2750-4ca8-8fc9-fc9c96fc82a7
- Local pid:
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pubs:698065
- Deposit date:
-
2017-06-01
Terms of use
- Copyright holder:
- Kaur et al
- Copyright date:
- 2017
- Notes:
- Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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