Genomes and Genes
Gene Symbol: HLA E
Description: major histocompatibility complex, class I, E
Alias: HLA-6.2, QA1, HLA class I histocompatibility antigen, alpha chain E, MHC class I antigen E, MHC class Ib antigen
Products: HLA E
- Greenberg M, Iafrate A, Skowronski J. The SH3 domain-binding surface and an acidic motif in HIV-1 Nef regulate trafficking of class I MHC complexes. EMBO J. 1998;17:2777-89 pubmed
- Le Gall S, Erdtmann L, Benichou S, Berlioz Torrent C, Liu L, Benarous R, et al. Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules. Immunity. 1998;8:483-95 pubmed..Nef interacts with the medium (mu) subunit of AP adaptor complexes involved in the recognition of tyrosine-based sorting signals, likely facilitating the connection between MHC I and the clathrin-dependent sorting machinery. ..
- Llano M, Lee N, Navarro F, Garcia P, Albar J, Geraghty D, et al. HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. Eur J Immunol. 1998;28:2854-63 pubmed..These results raise the possibility that CD94/NKG2-mediated recognition of HLA-E expressed on extravillous cytotrophoblasts plays an important role in maternal-fetal cellular interactions. ..
- Stevens J, Joly E, Trowsdale J, Butcher G. Peptide binding characteristics of the non-classical class Ib MHC molecule HLA-E assessed by a recombinant random peptide approach. BMC Immunol. 2001;2:5 pubmed
- King A, Allan D, Bowen M, Powis S, Joseph S, Verma S, et al. HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. Eur J Immunol. 2000;30:1623-31 pubmed
- Sullivan L, Clements C, Beddoe T, Johnson D, Hoare H, Lin J, et al. The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition. Immunity. 2007;27:900-11 pubmed
- Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard J. Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med. 1996;2:338-42 pubmed..The stimulation of MHC-I endocytosis by Nef represents a previously undocumented viral mechanism for evading the immune response. ..
- Atkins K, Thomas L, Youker R, Harriff M, Pissani F, You H, et al. HIV-1 Nef binds PACS-2 to assemble a multikinase cascade that triggers major histocompatibility complex class I (MHC-I) down-regulation: analysis using short interfering RNA and knock-out mice. J Biol Chem. 2008;283:11772-84 pubmed publisher..Together, these results demonstrate PACS-2 is required for Nef action and sorting of itinerant membrane cargo in the TGN/endosomal system. ..
- Nattermann J, Nischalke H, Hofmeister V, Ahlenstiel G, Zimmermann H, Leifeld L, et al. The HLA-A2 restricted T cell epitope HCV core 35-44 stabilizes HLA-E expression and inhibits cytolysis mediated by natural killer cells. Am J Pathol. 2005;166:443-53 pubmed..Our data indicate the existence of T cell epitopes that can be recognized by HLA-A2 and HLA-E. This dual recognition may contribute to viral persistence in hepatitis C...
- Marín R, Ruiz Cabello F, Pedrinaci S, Mendez R, Jimenez P, Geraghty D, et al. Analysis of HLA-E expression in human tumors. Immunogenetics. 2003;54:767-75 pubmed..The aberrant HLA-E expression might be of particular biological relevance in those HLA tumor phenotypes that express a single HLA-A allele when NK inhibition is markedly reduced due to the downregulation of HLA-B and -C alleles. ..
- Mazzarino P, Pietra G, Vacca P, Falco M, Colau D, Coulie P, et al. Identification of effector-memory CMV-specific T lymphocytes that kill CMV-infected target cells in an HLA-E-restricted fashion. Eur J Immunol. 2005;35:3240-7 pubmed..Our data suggest that HLA-E-restricted CTL may represent an additional effector cell type involved in defenses against HCMV, a virus which escapes the control exerted by conventional CTL or NK cells...
- Furukawa H, Yabe T, Akaza T, Tadokoro K, Tohma S, Inoue T, et al. Cell surface expression of HLA-E molecules on PBMC from a TAP1-deficient patient. Tissue Antigens. 1999;53:292-5 pubmed..These data suggest the existence of TAP-dependent and -independent pathways for the surface expression of HLA-E molecules...
- Lo Monaco E, Sibilio L, Melucci E, Tremante E, Suchanek M, Horejsi V, et al. HLA-E: strong association with beta2-microglobulin and surface expression in the absence of HLA class I signal sequence-derived peptides. J Immunol. 2008;181:5442-50 pubmed..Thus, HLA-E is a good, and not a poor, beta(2)m assembler, and TAP/tapasin-assisted ligand donation is only one, and possibly not even the major, pathway leading to its stabilization and surface expression. ..
- Mangasarian A, Foti M, Aiken C, Chin D, Carpentier J, Trono D. The HIV-1 Nef protein acts as a connector with sorting pathways in the Golgi and at the plasma membrane. Immunity. 1997;6:67-77 pubmed..Taken together, these data suggest that Nef down-regulates CD4 and probably MHC I by physically connecting these receptors with sorting pathways in the Golgi and at the plasma membrane...
- Wooden S, Kalb S, Cotter R, Soloski M. Cutting edge: HLA-E binds a peptide derived from the ATP-binding cassette transporter multidrug resistance-associated protein 7 and inhibits NK cell-mediated lysis. J Immunol. 2005;175:1383-7 pubmed..This report is the first to identify a non-MHC leader inhibitory peptide bound to HLA-E and provides insight into the immunoregulatory role of HLA-E during cell stress...
- Hoare H, Sullivan L, Pietra G, Clements C, Lee E, Ely L, et al. Structural basis for a major histocompatibility complex class Ib-restricted T cell response. Nat Immunol. 2006;7:256-64 pubmed
- Kaiser B, Pizarro J, Kerns J, Strong R. Structural basis for NKG2A/CD94 recognition of HLA-E. Proc Natl Acad Sci U S A. 2008;105:6696-701 pubmed publisher..Thus, the evolution of the NKG2x/CD94 family of receptors has likely been shaped both by the need to bind the invariant HLA-E ligand and the need to avoid subversion by pathogen-derived decoys. ..
- Zeng X, Chen H, Gupta R, Paz Altschul O, Bowcock A, Liao W. Deletion of the activating NKG2C receptor and a functional polymorphism in its ligand HLA-E in psoriasis susceptibility. Exp Dermatol. 2013;22:679-81 pubmed publisher..Our findings support a potential immunoregulatory role for NK cells in psoriasis and suggest the importance of future studies to investigate the contribution of NK cells and their regulatory receptors to the pathogenesis of psoriasis. ..
- Menier C, Saez B, Horejsi V, Martinozzi S, Krawice Radanne I, Bruel S, et al. Characterization of monoclonal antibodies recognizing HLA-G or HLA-E: new tools to analyze the expression of nonclassical HLA class I molecules. Hum Immunol. 2003;64:315-26 pubmed..These new mAbs represent valuable tools to study the expression of HLA-G and HLA-E molecules in cells and tissues under normal and pathologic conditions. ..
- Brooks A, Borrego F, Posch P, Patamawenu A, Scorzelli C, Ulbrecht M, et al. Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells. J Immunol. 1999;162:305-13 pubmed..Thus CD94/NKG2A recognition of HLA-E is controlled by peptide at two levels; first, peptide must stabilize HLA-E and promote cell surface expression, and second, the HLA-E/peptide complex must form the ligand for CD94/NKG2A. ..
- Akari H, Arold S, Fukumori T, Okazaki T, Strebel K, Adachi A. Nef-induced major histocompatibility complex class I down-regulation is functionally dissociated from its virion incorporation, enhancement of viral infectivity, and CD4 down-regulation. J Virol. 2000;74:2907-12 pubmed
- Braud V, Allan D, O Callaghan C, Soderstrom K, D ANDREA A, Ogg G, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998;391:795-9 pubmed
- Kirchhoff F, Schindler M, Specht A, Arhel N, Munch J. Role of Nef in primate lentiviral immunopathogenesis. Cell Mol Life Sci. 2008;65:2621-36 pubmed publisher..This evolutionary loss of a specific Nef function may contribute to the high virulence of HIV-1 in humans. ..
- Blagoveshchenskaya A, Thomas L, Feliciangeli S, Hung C, Thomas G. HIV-1 Nef downregulates MHC-I by a PACS-1- and PI3K-regulated ARF6 endocytic pathway. Cell. 2002;111:853-66 pubmed..These data provide new insights into the cellular basis of HIV-1 immunoevasion. ..
- PURCELL S, Wray N, Stone J, Visscher P, O Donovan M, Sullivan P, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460:748-52 pubmed publisher..We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases. ..
- Gudbjartsson D, Bjornsdottir U, Halapi E, Helgadottir A, Sulem P, Jonsdottir G, et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 2009;41:342-7 pubmed publisher..2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls). ..
- Vance R, Kraft J, Altman J, Jensen P, Raulet D. Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). J Exp Med. 1998;188:1841-8 pubmed..Our findings suggest that mouse NK cells, like their human counterparts, use multiple mechanisms to survey class I expression on target cells. ..
- Danzer M, Polin H, Pröll J, Haunschmid R, Hofer K, Stabentheiner S, et al. Clinical significance of HLA-E*0103 homozygosity on survival after allogeneic hematopoietic stem-cell transplantation. Transplantation. 2009;88:528-32 pubmed publisher..The risk of posttransplant complications was significantly reduced when the donor possesses the HLA-E*0103, 0103 genotype, and this was translated in a better overall survival. ..
- Swann S, Williams M, Story C, Bobbitt K, Fleis R, Collins K. HIV-1 Nef blocks transport of MHC class I molecules to the cell surface via a PI 3-kinase-dependent pathway. Virology. 2001;282:267-77 pubmed..We propose that Nef diverts MHC-1 proteins into a PI 3-kinase-dependent transport pathway that prevents expression on the cell surface. ..
- Furst D, Bindja J, Arnold R, Herr W, Schwerdtfeger R, Muller C, et al. HLA-E polymorphisms in hematopoietic stem cell transplantation. Tissue Antigens. 2012;79:287-90 pubmed publisher..We could not confirm any of the previous observations in our cohort and consider it unlikely that HLA-E polymorphisms affect outcome of HSCT. ..
- Benevolo M, Mottolese M, Tremante E, Rollo F, Diodoro M, Ercolani C, et al. High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis. J Transl Med. 2011;9:184 pubmed publisher..It is implied that this process occurs stepwise, as predicted by the widely accepted 'immunoediting' model. ..
- Schaefer M, Wonderlich E, Roeth J, Leonard J, Collins K. HIV-1 Nef targets MHC-I and CD4 for degradation via a final common beta-COP-dependent pathway in T cells. PLoS Pathog. 2008;4:e1000131 pubmed publisher..The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef. ..
- Nattermann J, Nischalke H, Hofmeister V, Kupfer B, Ahlenstiel G, Feldmann G, et al. HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells. Antivir Ther. 2005;10:95-107 pubmed..These results propose HIV-mediated up-regulation of HLA-E expression as an additional evasion strategy targeting the antiviral activities of NK cells, which may contribute to the capability of the virus in establishing chronic infection...
- Levy E, Bianchini M, von Euw E, Barrio M, Bravo A, Furman D, et al. Human leukocyte antigen-E protein is overexpressed in primary human colorectal cancer. Int J Oncol. 2008;32:633-41 pubmed..Furthermore, we showed that upregulation of HLA-E could be a marker of shorter disease-free survival in Dukes' C patients and we suggest that this molecule renders tumours less susceptible to immune attack. ..
- Le Gall S, Buseyne F, Trocha A, Walker B, Heard J, Schwartz O. Distinct trafficking pathways mediate Nef-induced and clathrin-dependent major histocompatibility complex class I down-regulation. J Virol. 2000;74:9256-66 pubmed..Moreover, trafficking of A2-endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef. Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation. ..
- Noviello C, Benichou S, Guatelli J. Cooperative binding of the class I major histocompatibility complex cytoplasmic domain and human immunodeficiency virus type 1 Nef to the endosomal AP-1 complex via its mu subunit. J Virol. 2008;82:1249-58 pubmed..The data support a cooperative binding model in which Nef functions as a clathrin-associated sorting protein that allows recognition of an incomplete, tyrosine-based mu-binding signal in the MHC-I CD by AP-1. ..
- Derre L, Corvaisier M, Charreau B, Moreau A, Godefroy E, Moreau Aubry A, et al. Expression and release of HLA-E by melanoma cells and melanocytes: potential impact on the response of cytotoxic effector cells. J Immunol. 2006;177:3100-7 pubmed..The biological significance of these findings warrants further investigation. ..
- Ulbrecht M, Honka T, Person S, Johnson J, Weiss E. The HLA-E gene encodes two differentially regulated transcripts and a cell surface protein. J Immunol. 1992;149:2945-53 pubmed..These results indicate that the HLA-E gene codes for a class I H chain that can be expressed on the cell surface. ..
- O Callaghan C, Tormo J, Willcox B, Braud V, Jakobsen B, Stuart D, et al. Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E. Mol Cell. 1998;1:531-41 pubmed..These molecular adaptations make HLA-E a rigorous checkpoint at the cell surface reporting on the integrity of the antigen processing pathway to CD94/NKG2 receptor-bearing natural killer cells. ..
- Peng B, Robert Guroff M. Deletion of N-terminal myristoylation site of HIV Nef abrogates both MHC-1 and CD4 down-regulation. Immunol Lett. 2001;78:195-200 pubmed..Non-myristoylated Nef containing a full complement of CTL epitopes has greater potential as a vaccine component than wild-type Nef. ..
- de Kruijf E, Sajet A, van Nes J, Natanov R, Putter H, Smit V, et al. HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol. 2010;185:7452-9 pubmed publisher..These results provide further evidence that breast cancer is immunogenic, but also capable of evading tumor eradication by the host's immune system, by up- or downregulation of HLA class Ia and class Ib loci. ..
- Garcia P, Llano M, de Heredia A, Willberg C, Caparros E, Aparicio P, et al. Human T cell receptor-mediated recognition of HLA-E. Eur J Immunol. 2002;32:936-44 pubmed..Altogether, the data unequivocally imply the generation of human T cells potentially recognizing through the alpha beta TCR HLA-E molecules that bind to class I- and virus-derived peptides...
- Braud V, Allan D, Wilson D, McMichael A. TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol. 1998;8:1-10 pubmed..Our results also show that, although these HLA-E binding peptides are derived from signal sequences, they may be released back into the cytosol and subsequently translocated by the TAP complex and loaded onto HLA-E molecules. ..
- Palmisano G, Contardi E, Morabito A, Gargaglione V, Ferrara G, Pistillo M. HLA-E surface expression is independent of the availability of HLA class I signal sequence-derived peptides in human tumor cell lines. Hum Immunol. 2005;66:1-12 pubmed
- Lin Y, Wan L, Wu J, Sheu J, Lin C, Lan Y, et al. HLA-E gene polymorphism associated with susceptibility to Kawasaki disease and formation of coronary artery aneurysms. Arthritis Rheum. 2009;60:604-10 pubmed publisher..Our results suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of KD. ..
- Stangl S, Gross C, Pockley A, ASEA A, Multhoff G. Influence of Hsp70 and HLA-E on the killing of leukemic blasts by cytokine/Hsp70 peptide-activated human natural killer (NK) cells. Cell Stress Chaperones. 2008;13:221-30 pubmed publisher..These findings indicate that Hsp70 (as an activatory molecule) and HLA-E (as an inhibitory ligand) expression influence the susceptibility of leukemic cells to the cytolytic activities of cytokine/TKD-activated NK cells. ..
- Petrie E, Clements C, Lin J, Sullivan L, Johnson D, Huyton T, et al. CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. J Exp Med. 2008;205:725-35 pubmed publisher..Differences in the docking strategies used by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the promiscuous nature of ligand recognition by NKG2D compared with the fidelity of the CD94-NKG2 receptors. ..
- Houchins J, Lanier L, Niemi E, Phillips J, Ryan J. Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J Immunol. 1997;158:3603-9 pubmed..These data indicate that NKG2-A and NKG2-C deliver, respectively, inhibitory and activating transmembrane signals in NK cells. ..
- Heinzel A, Grotzke J, Lines R, Lewinsohn D, McNabb A, Streblow D, et al. HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med. 2002;196:1473-81 pubmed..This is the first demonstration of the ability of HLA-E to present pathogen-derived antigen. Further definition of the HLA-E specific response may aid development of an effective vaccine against tuberculosis. ..
- Jiang H, Canfield S, Gallagher M, Jiang H, Jiang Y, Zheng Z, et al. HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J Clin Invest. 2010;120:3641-50 pubmed publisher..These data suggest that HLA-E-restricted CD8(+) T cells may play an important role in keeping self-reactive T cells in check. Thus, correction of this defect could be a potentially effective and safe approach in the therapy of T1D. ..
- Wei X, Orr H. Differential expression of HLA-E, HLA-F, and HLA-G transcripts in human tissue. Hum Immunol. 1990;29:131-42 pubmed..These results raise the intriguing possibility that the HLA-G-encoded molecule has a role in embryonic development and/or the fetal-maternal immune response. ..
- Strong R, Holmes M, Li P, Braun L, Lee N, Geraghty D. HLA-E allelic variants. Correlating differential expression, peptide affinities, crystal structures, and thermal stabilities. J Biol Chem. 2003;278:5082-90 pubmed..This in turn may help explain the apparent balancing selection acting on this locus. ..
- Williams M, Roeth J, Kasper M, Fleis R, Przybycin C, Collins K. Direct binding of human immunodeficiency virus type 1 Nef to the major histocompatibility complex class I (MHC-I) cytoplasmic tail disrupts MHC-I trafficking. J Virol. 2002;76:12173-84 pubmed..In addition, they provide the first direct evidence indicating that Nef functions as an adaptor molecule able to link MHC-I to cellular trafficking proteins. ..
- Baugh L, Garcia J, Foster J. Functional characterization of the human immunodeficiency virus type 1 Nef acidic domain. J Virol. 2008;82:9657-67 pubmed publisher..Our results are consistent with an alternative model in which (62)EEEE(65) plays a stabilizing role in the formation of a ternary complex between Nef, the MHC-I cytoplasmic domain, and AP-1. ..