Structural and regulatory diversity shape HLA-C protein expression levels

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Structural and regulatory diversity shape HLA-C protein expression levels. / Kaur, Gurman; Gras, Stephanie; Mobbs, Jesse I; Vivian, Julian P; Cortes, Adrian; Barber, Thomas; Kuttikkatte, Subita Balaram; Jensen, Lise Torp; Attfield, Kathrine E; Dendrou, Calliope A; Carrington, Mary; McVean, Gil; Purcell, Anthony W; Rossjohn, Jamie; Fugger, Lars.

In: Nature Communications, Vol. 8, 26.06.2017, p. 15924.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Kaur, G, Gras, S, Mobbs, JI, Vivian, JP, Cortes, A, Barber, T, Kuttikkatte, SB, Jensen, LT, Attfield, KE, Dendrou, CA, Carrington, M, McVean, G, Purcell, AW, Rossjohn, J & Fugger, L 2017, 'Structural and regulatory diversity shape HLA-C protein expression levels', Nature Communications, vol. 8, pp. 15924. https://doi.org/10.1038/ncomms15924

APA

Kaur, G., Gras, S., Mobbs, J. I., Vivian, J. P., Cortes, A., Barber, T., Kuttikkatte, S. B., Jensen, L. T., Attfield, K. E., Dendrou, C. A., Carrington, M., McVean, G., Purcell, A. W., Rossjohn, J., & Fugger, L. (2017). Structural and regulatory diversity shape HLA-C protein expression levels. Nature Communications, 8, 15924. https://doi.org/10.1038/ncomms15924

CBE

Kaur G, Gras S, Mobbs JI, Vivian JP, Cortes A, Barber T, Kuttikkatte SB, Jensen LT, Attfield KE, Dendrou CA, Carrington M, McVean G, Purcell AW, Rossjohn J, Fugger L. 2017. Structural and regulatory diversity shape HLA-C protein expression levels. Nature Communications. 8:15924. https://doi.org/10.1038/ncomms15924

MLA

Vancouver

Kaur G, Gras S, Mobbs JI, Vivian JP, Cortes A, Barber T et al. Structural and regulatory diversity shape HLA-C protein expression levels. Nature Communications. 2017 Jun 26;8:15924. https://doi.org/10.1038/ncomms15924

Author

Kaur, Gurman ; Gras, Stephanie ; Mobbs, Jesse I ; Vivian, Julian P ; Cortes, Adrian ; Barber, Thomas ; Kuttikkatte, Subita Balaram ; Jensen, Lise Torp ; Attfield, Kathrine E ; Dendrou, Calliope A ; Carrington, Mary ; McVean, Gil ; Purcell, Anthony W ; Rossjohn, Jamie ; Fugger, Lars. / Structural and regulatory diversity shape HLA-C protein expression levels. In: Nature Communications. 2017 ; Vol. 8. pp. 15924.

Bibtex

@article{6bbf2508b9aa4303bb72ae00a767898c,
title = "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 analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression.",
keywords = "Journal Article",
author = "Gurman Kaur and Stephanie Gras and Mobbs, {Jesse I} and Vivian, {Julian P} and Adrian Cortes and Thomas Barber and Kuttikkatte, {Subita Balaram} and Jensen, {Lise Torp} and Attfield, {Kathrine E} and Dendrou, {Calliope A} and Mary Carrington and Gil McVean and Purcell, {Anthony W} and Jamie Rossjohn and Lars Fugger",
year = "2017",
month = jun,
day = "26",
doi = "10.1038/ncomms15924",
language = "English",
volume = "8",
pages = "15924",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Structural and regulatory diversity shape HLA-C protein expression levels

AU - Kaur, Gurman

AU - Gras, Stephanie

AU - Mobbs, Jesse I

AU - Vivian, Julian P

AU - Cortes, Adrian

AU - Barber, Thomas

AU - Kuttikkatte, Subita Balaram

AU - Jensen, Lise Torp

AU - Attfield, Kathrine E

AU - Dendrou, Calliope A

AU - Carrington, Mary

AU - McVean, Gil

AU - Purcell, Anthony W

AU - Rossjohn, Jamie

AU - Fugger, Lars

PY - 2017/6/26

Y1 - 2017/6/26

N2 - 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 analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression.

AB - 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 analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression.

KW - Journal Article

U2 - 10.1038/ncomms15924

DO - 10.1038/ncomms15924

M3 - Journal article

C2 - 28649982

VL - 8

SP - 15924

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

ER -