5vge › Citations

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

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
Nat Commun 8 15924 (2017)
Cited: 65 times
EuropePMC logo PMID: 28649982

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.

Articles - 5vge mentioned but not cited (16)

  1. Structural and regulatory diversity shape HLA-C protein expression levels. 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. Nat Commun 8 15924 (2017)
  2. The molecular basis for peptide repertoire selection in the human leucocyte antigen (HLA) C*06:02 molecule. Mobbs JI, Illing PT, Dudek NL, Brooks AG, Baker DG, Purcell AW, Rossjohn J, Vivian JP. J Biol Chem 292 17203-17215 (2017)
  3. Immunoinformatic approach to assess SARS-CoV-2 protein S epitopes recognised by the most frequent MHC-I alleles in the Brazilian population. Moura RR, Agrelli A, Santos-Silva CA, Silva N, Assunção BR, Brandão L, Benko-Iseppon AM, Crovella S. J Clin Pathol 74 528-532 (2021)
  4. An Immunoinformatics Approach for SARS-CoV-2 in Latam Populations and Multi-Epitope Vaccine Candidate Directed towards the World's Population. Cuspoca AF, Díaz LL, Acosta AF, Peñaloza MK, Méndez YR, Clavijo DC, Yosa Reyes J. Vaccines (Basel) 9 581 (2021)
  5. Computational perspectives revealed prospective vaccine candidates from five structural proteins of novel SARS corona virus 2019 (SARS-CoV-2). Anand R, Biswal S, Bhatt R, Tiwary BN. PeerJ 8 e9855 (2020)
  6. Vaccinomics approach for scheming potential epitope-based peptide vaccine by targeting l-protein of Marburg virus. Pervin T, Oany AR. In Silico Pharmacol 9 21 (2021)
  7. A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus. Kibria KMK, Faruque MO, Islam MSB, Ullah H, Mahmud S, Miah M, Saleh AA. Appl Microbiol Biotechnol 106 4091-4114 (2022)
  8. HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. Shimizu C, Kim J, Eleftherohorinou H, Wright VJ, Hoang LT, Tremoulet AH, Franco A, Hibberd ML, Takahashi A, Kubo M, Ito K, Tanaka T, Onouchi Y, Coin LJM, Levin M, Burns JC, Shike H, International Kawasaki Disease Genetic Consortium. Hum Immunol 80 731-738 (2019)
  9. A comprehensive analysis of amino-peptidase N1 protein (APN) from Anopheles culicifacies for epitope design using Immuno-informatics models. Jakhar R, Kumar P, Sehrawat N, Gakhar SK. Bioinformation 15 600-612 (2019)
  10. Fine-mapping studies distinguish genetic risks for childhood- and adult-onset asthma in the HLA region. Clay SM, Schoettler N, Goldstein AM, Carbonetto P, Dapas M, Altman MC, Rosasco MG, Gern JE, Jackson DJ, Im HK, Stephens M, Nicolae DL, Ober C. Genome Med 14 55 (2022)
  11. Hemizygous amplification and complete Sanger sequencing of HLA-C*07:37:01:02 from a South European Caucasoid. Asenjo J, Cisneros E, Vilches C. HLA 97 159-161 (2021)
  12. 21-Hydroxylase-Specific CD8+ T Cells in Autoimmune Addison's Disease Are Restricted by HLA-A2 and HLA-C7 Molecules. Hellesen A, Aslaksen S, Breivik L, Røyrvik EC, Bruserud Ø, Edvardsen K, Brokstad KA, Wolff ASB, Husebye ES, Bratland E. Front Immunol 12 742848 (2021)
  13. Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules. Papadaki GF, Ani O, Florio TJ, Young MC, Danon JN, Sun Y, Dersh D, Sgourakis NG. Front Immunol 14 1116906 (2023)
  14. T cells discriminate between groups C1 and C2 HLA-C. Sim MJW, Stotz Z, Lu J, Brennan P, Long EO, Sun PD. Elife 11 e75670 (2022)
  15. research-article The landscape of MHC-presented phosphopeptides yields actionable shared tumor antigens for cancer immunotherapy across multiple HLA alleles. Molvi Z, Klatt MG, Dao T, Urraca J, Scheinberg DA, O'Reilly RJ. bioRxiv 2023.02.08.527552 (2023)
  16. The landscape of MHC-presented phosphopeptides yields actionable shared tumor antigens for cancer immunotherapy across multiple HLA alleles. Molvi Z, Klatt MG, Dao T, Urraca J, Scheinberg DA, O'Reilly RJ. J Immunother Cancer 11 e006889 (2023)


Reviews citing this publication (15)

  1. HLA variation and disease. Dendrou CA, Petersen J, Rossjohn J, Fugger L. Nat Rev Immunol 18 325-339 (2018)
  2. Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR. Dehn J, Spellman S, Hurley CK, Shaw BE, Barker JN, Burns LJ, Confer DL, Eapen M, Fernandez-Vina M, Hartzman R, Maiers M, Marino SR, Mueller C, Perales MA, Rajalingam R, Pidala J. Blood 134 924-934 (2019)
  3. The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface. Papúchová H, Meissner TB, Li Q, Strominger JL, Tilburgs T. Front Immunol 10 2730 (2019)
  4. Genetics of antigen processing and presentation. Kelly A, Trowsdale J. Immunogenetics 71 161-170 (2019)
  5. Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies. Akcay IM, Katrinli S, Ozdil K, Doganay GD, Doganay L. World J Gastroenterol 24 3347-3360 (2018)
  6. Molecular evolution of elements controlling HLA-C expression: Adaptation to a role as a killer-cell immunoglobulin-like receptor ligand regulating natural killer cell function. Anderson SK. HLA 92 271-278 (2018)
  7. Tuning of human NK cells by endogenous HLA-C expression. Goodson-Gregg FJ, Krepel SA, Anderson SK. Immunogenetics 72 205-215 (2020)
  8. Monkeying Around: Using Non-human Primate Models to Study NK Cell Biology in HIV Infections. Manickam C, Shah SV, Nohara J, Ferrari G, Reeves RK. Front Immunol 10 1124 (2019)
  9. From Chickens to Humans: The Importance of Peptide Repertoires for MHC Class I Alleles. Kaufman J. Front Immunol 11 601089 (2020)
  10. HLA imputation and its application to genetic and molecular fine-mapping of the MHC region in autoimmune diseases. Naito T, Okada Y. Semin Immunopathol 44 15-28 (2022)
  11. Principles of Virtual Crossmatch Testing for Kidney Transplantation. Bhaskaran MC, Heidt S, Muthukumar T. Kidney Int Rep 7 1179-1188 (2022)
  12. Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients. Dubreuil L, Chevallier P, Retière C, Gagne K. Cancers (Basel) 13 3767 (2021)
  13. The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity. Vollmers S, Lobermeyer A, Körner C. Cells 10 3108 (2021)
  14. HLA allele-specific expression: Methods, disease associations, and relevance in hematopoietic stem cell transplantation. Johansson T, Partanen J, Saavalainen P. Front Immunol 13 1007425 (2022)
  15. "HLA-C: evolution, epigenetics, and pathological implications in the major histocompatibility complex". Velastegui E, Vera E, Vanden Berghe W, Muñoz MS, Orellana-Manzano A. Front Genet 14 1206034 (2023)

Articles citing this publication (34)

  1. A large peptidome dataset improves HLA class I epitope prediction across most of the human population. Sarkizova S, Klaeger S, Le PM, Li LW, Oliveira G, Keshishian H, Hartigan CR, Zhang W, Braun DA, Ligon KL, Bachireddy P, Zervantonakis IK, Rosenbluth JM, Ouspenskaia T, Law T, Justesen S, Stevens J, Lane WJ, Eisenhaure T, Lan Zhang G, Clauser KR, Hacohen N, Carr SA, Wu CJ, Keskin DB. Nat Biotechnol 38 199-209 (2020)
  2. Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity. DeWitt WS, Smith A, Schoch G, Hansen JA, Matsen FA, Bradley P. Elife 7 e38358 (2018)
  3. Binding affinities of 438 HLA proteins to complete proteomes of seven pandemic viruses and distributions of strongest and weakest HLA peptide binders in populations worldwide. Barquera R, Collen E, Di D, Buhler S, Teixeira J, Llamas B, Nunes JM, Sanchez-Mazas A. HLA 96 277-298 (2020)
  4. High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D. Sim MJW, Lu J, Spencer M, Hopkins F, Tran E, Rosenberg SA, Long EO, Sun PD. Proc Natl Acad Sci U S A 117 12826-12835 (2020)
  5. Expression estimation and eQTL mapping for HLA genes with a personalized pipeline. Aguiar VRC, César J, Delaneau O, Dermitzakis ET, Meyer D. PLoS Genet 15 e1008091 (2019)
  6. Human NK cell receptor KIR2DS4 detects a conserved bacterial epitope presented by HLA-C. Sim MJW, Rajagopalan S, Altmann DM, Boyton RJ, Sun PD, Long EO. Proc Natl Acad Sci U S A 116 12964-12973 (2019)
  7. The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases. Vizcaíno JA, Kubiniok P, Kovalchik KA, Ma Q, Duquette JD, Mongrain I, Deutsch EW, Peters B, Sette A, Sirois I, Caron E. Mol Cell Proteomics 19 31-49 (2020)
  8. Discrimination Between Human Leukocyte Antigen Class I-Bound and Co-Purified HIV-Derived Peptides in Immunopeptidomics Workflows. Partridge T, Nicastri A, Kliszczak AE, Yindom LM, Kessler BM, Ternette N, Borrow P. Front Immunol 9 912 (2018)
  9. Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method. Yamamoto F, Suzuki S, Mizutani A, Shigenari A, Ito S, Kametani Y, Kato S, Fernandez-Viña M, Murata M, Morishima S, Morishima Y, Tanaka M, Kulski JK, Bahram S, Shiina T. Front Immunol 11 941 (2020)
  10. Cross-Reactivity of Virus-Specific CD8+ T Cells Against Allogeneic HLA-C: Possible Implications for Pregnancy Outcome. van der Zwan A, van der Meer-Prins EMW, van Miert PPMC, van den Heuvel H, Anholts JDH, Roelen DL, Claas FHJ, Heidt S. Front Immunol 9 2880 (2018)
  11. An immunogenetic view of COVID-19. Aguiar VRC, Augusto DG, Castelli EC, Hollenbach JA, Meyer D, Nunes K, Petzl-Erler ML. Genet Mol Biol 44 e20210036 (2021)
  12. HLA RNA Sequencing With Unique Molecular Identifiers Reveals High Allele-Specific Variability in mRNA Expression. Johansson T, Yohannes DA, Koskela S, Partanen J, Saavalainen P. Front Immunol 12 629059 (2021)
  13. ERAP1 Controls the Autoimmune Response against Melanocytes in Psoriasis by Generating the Melanocyte Autoantigen and Regulating Its Amount for HLA-C*06:02 Presentation. Arakawa A, Reeves E, Vollmer S, Arakawa Y, He M, Galinski A, Stöhr J, Dornmair K, James E, Prinz JC. J Immunol 207 2235-2244 (2021)
  14. Precision Neoantigen Discovery Using Large-scale Immunopeptidomes and Composite Modeling of MHC Peptide Presentation. Pyke RM, Mellacheruvu D, Dea S, Abbott CW, Zhang SV, Phillips NA, Harris J, Bartha G, Desai S, McClory R, West J, Snyder MP, Chen R, Boyle SM. Mol Cell Proteomics 20 100111 (2021)
  15. Stability and Expression Levels of HLA-C on the Cell Membrane Modulate HIV-1 Infectivity. Parolini F, Biswas P, Serena M, Sironi F, Muraro V, Guizzardi E, Cazzoletti L, Scupoli MT, Gibellini D, Ugolotti E, Biassoni R, Beretta A, Malnati M, Romanelli MG, Zipeto D. J Virol 92 e01711-17 (2018)
  16. Thermostability profiling of MHC-bound peptides: a new dimension in immunopeptidomics and aid for immunotherapy design. Jappe EC, Garde C, Ramarathinam SH, Passantino E, Illing PT, Mifsud NA, Trolle T, Kringelum JV, Croft NP, Purcell AW. Nat Commun 11 6305 (2020)
  17. Negative trade-off between neoantigen repertoire breadth and the specificity of HLA-I molecules shapes antitumor immunity. Manczinger M, Koncz B, Balogh GM, Papp BT, Asztalos L, Kemény L, Papp B, Pál C. Nat Cancer 2 950-961 (2021)
  18. Tuning of NK-Specific HLA-C Expression by Alternative mRNA Splicing. Goodson-Gregg FJ, Rothbard B, Zhang A, Wright PW, Li H, Walker-Sperling VE, Carrington M, Anderson SK. Front Immunol 10 3034 (2019)
  19. HIV-1-Associated Neurocognitive Disorders: Is HLA-C Binding Stability to β2-Microglobulin a Missing Piece of the Pathogenetic Puzzle? Zipeto D, Serena M, Mutascio S, Parolini F, Diani E, Guizzardi E, Muraro V, Lattuada E, Rizzardo S, Malena M, Lanzafame M, Malerba G, Romanelli MG, Tamburin S, Gibellini D. Front Neurol 9 791 (2018)
  20. Late antibody-mediated rejection in a kidney transplant recipient: COVID 19 induced? Nourié N, Nassereddine H, Mouawad S, Chebbou L, Ghaleb R, Abbas F, Azar H. BMC Nephrol 23 91 (2022)
  21. Comparison between qPCR and RNA-seq reveals challenges of quantifying HLA expression. Aguiar VRC, Castelli EC, Single RM, Bashirova A, Ramsuran V, Kulkarni S, Augusto DG, Martin MP, Gutierrez-Arcelus M, Carrington M, Meyer D. Immunogenetics 75 249-262 (2023)
  22. Comprehensive analysis of circular RNA in oral leukoplakia: upregulated circHLA-C as a potential biomarker for diagnosis and prognosis. Xu S, Song Y, Shao Y, Zhou H. Ann Transl Med 8 1375 (2020)
  23. HLA Class II Presentation Is Specifically Altered at Elevated Temperatures in the B-Lymphoblastic Cell Line JY. Demmers LC, Wu W, Heck AJR. Mol Cell Proteomics 20 100089 (2021)
  24. Host KIR/HLA-C Genotypes Determine HIV-Mediated Changes of the NK Cell Repertoire and Are Associated With Vpu Sequence Variations Impacting Downmodulation of HLA-C. Vollmers S, Lobermeyer A, Niehrs A, Fittje P, Indenbirken D, Nakel J, Virdi S, Brias S, Trenkner T, Sauer G, Peine S, Behrens GMN, Lehmann C, Meurer A, Pauli R, Postel N, Roider J, Scholten S, Spinner CD, Stephan C, Wolf E, Wyen C, Richert L, Norman PJ, Sauter J, Schmidt AH, Hoelzemer A, Altfeld M, Körner C. Front Immunol 13 922252 (2022)
  25. HLA-C*12:02 is strongly associated with Xuesaitong-induced cutaneous adverse drug reactions. Yan S, Xiong H, Shao F, Zhang W, Yang F, Qi Z, Chen S, He L, Jiang M, Su Y, Zhu H, Qin S, Zhu Q, Luo X, Xing Q. Pharmacogenomics J 19 277-285 (2019)
  26. High cell surface expression and peptide binding affinity of HLA-DQA1*05:03, a susceptible allele of neuromyelitis optica spectrum disorders (NMOSD). Beppu S, Kinoshita M, Wilamowski J, Suenaga T, Yasumizu Y, Ogawa K, Ishikura T, Tada S, Koda T, Murata H, Shiraishi N, Sugiyama Y, Kihara K, Sugimoto T, Arase H, Standley DM, Okuno T, Mochizuki H. Sci Rep 12 106 (2022)
  27. Immunogenetic factors in early immune control of human immunodeficiency virus type 1 (HIV-1) infection: Evaluation of HLA class I amino acid variants in two African populations. Wiener HW, Shrestha S, Lu H, Karita E, Kilembe W, Allen S, Hunter E, Goepfert PA, Tang J. Hum Immunol 79 166-171 (2018)
  28. Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes. Camacho-Bydume C, Wang T, Sees JA, Fernandez-Viña M, Abid MB, Askar M, Beitinjaneh A, Brown V, Castillo P, Chhabra S, Gadalla SM, Hsu JM, Kamoun M, Lazaryan A, Nishihori T, Page K, Schetelig J, Fleischhauer K, Marsh SGE, Paczesny S, Spellman SR, Lee SJ, Hsu KC. Transplant Cell Ther 27 142.e1-142.e11 (2021)
  29. Association between HLA-C alleles and COVID-19 severity in a pilot study with a Spanish Mediterranean Caucasian cohort. Vigón L, Galán M, Torres M, Martín-Galiano AJ, Rodríguez-Mora S, Mateos E, Corona M, Malo R, Navarro C, Murciano-Antón MA, García-Gutiérrez V, Planelles V, Martínez-Laso J, López-Huertas MR, Coiras M, Multidisciplinary Group of Study of COVID-19 (MGS-COVID). PLoS One 17 e0272867 (2022)
  30. Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution. Kang JB, Shen AZ, Gurajala S, Nathan A, Rumker L, Aguiar VRC, Valencia C, Lagattuta KA, Zhang F, Jonsson AH, Yazar S, Alquicira-Hernandez J, Khalili H, Ananthakrishnan AN, Jagadeesh K, Dey K, Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Daly MJ, Xavier RJ, Donlin LT, Anolik JH, Powell JE, Rao DA, Brenner MB, Gutierrez-Arcelus M, Luo Y, Sakaue S, Raychaudhuri S. Nat Genet 55 2255-2268 (2023)
  31. Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade. Kaur G, Porter CBM, Ashenberg O, Lee J, Riesenfeld SJ, Hofree M, Aggelakopoulou M, Subramanian A, Kuttikkatte SB, Attfield KE, Desel CAE, Davies JL, Evans HG, Avraham-Davidi I, Nguyen LT, Dionne DA, Neumann AE, Jensen LT, Barber TR, Soilleux E, Carrington M, McVean G, Rozenblatt-Rosen O, Regev A, Fugger L. Nat Commun 13 4398 (2022)
  32. Precision Neoantigen Discovery Using Large-Scale Immunopeptidomes and Composite Modeling of MHC Peptide Presentation. Pyke RM, Mellacheruvu D, Dea S, Abbott C, Zhang SV, Phillips NA, Harris J, Bartha G, Desai S, McClory R, West J, Snyder MP, Chen R, Boyle SM. Mol Cell Proteomics 22 100506 (2023)
  33. Proteogenomics Reveal the Overexpression of HLA-I in Cancer. Wang Y, Fenyö D. J Proteome Res 22 3625-3639 (2023)
  34. The complex HLA-E-nonapeptide in Behçet disease. Castaño-Núñez ÁL, Montes-Cano MA, García-Lozano JR, Ortego-Centeno N, García-Hernández FJ, Espinosa G, Graña-Gil G, Sánchez-Bursón J, Juliá MR, Solans R, Blanco R, Barnosi-Marín AC, Gómez de la Torre R, Fanlo P, Rodríguez-Carballeira M, Rodríguez-Rodríguez L, Camps T, Castañeda S, Alegre-Sancho JJ, Martín J, González-Escribano MF. Front Immunol 14 1080047 (2023)


Quick links