HLA-F

HLA-F
Identifiers
Aliases	HLA-F , CDA12, HLA-5.4, HLA-CDA12, major histocompatibility complex, class I, F
External IDs	OMIM: 143110 MGI: 3647514 HomoloGene: 133121 GeneCards: HLA-F
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p22.1 Start 29,722,775 bp [1] End 29,738,528 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in spleen blood lymph node appendix monocyte right lung duodenum upper lobe of left lung bone marrow cells gallbladder n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function TAP2 binding TAP1 binding signaling receptor binding peptide antigen binding protein binding beta-2-microglobulin binding 14-3-3 protein binding Cellular component integral component of membrane phagocytic vesicle membrane early endosome membrane membrane Golgi membrane plasma membrane cell surface endoplasmic reticulum MHC class I protein complex ER to Golgi transport vesicle membrane integral component of lumenal side of endoplasmic reticulum membrane recycling endosome membrane extracellular space lysosome lysosomal membrane endosome external side of plasma membrane MHC class Ib protein complex Biological process antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent interferon-gamma-mediated signaling pathway immune system process antigen processing and presentation of peptide antigen via MHC class I antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent type I interferon signaling pathway regulation of immune response positive regulation of T cell mediated cytotoxicity antigen processing and presentation of endogenous peptide antigen via MHC class Ib immune response antigen processing and presentation of exogenous peptide antigen via MHC class Ib antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent negative regulation of T cell cytokine production negative regulation of natural killer cell cytokine production positive regulation of natural killer cell cytokine production negative regulation of natural killer cell degranulation positive regulation of natural killer cell degranulation negative regulation of natural killer cell mediated cytotoxicity negative regulation of neuron death Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3134 630294 Ensembl ENSG00000229698 ENSG00000237508 ENSG00000234487 ENSG00000206509 ENSG00000137403 ENSG00000235220 ENSG00000204642 n/a UniProt P30511 Q0WXH6 RefSeq (mRNA) NM_001098478 NM_001098479 NM_018950 NM_001177467 RefSeq (protein) NP_001091948 NP_001091949 NP_061823 NP_001170938 Location (UCSC) Chr 6: 29.72 – 29.74 Mb n/a PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. ^{[4] [5]} It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include IFN-gamma signaling and CDK-mediated phosphorylation (cyclin-dependent kinase) and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication. ^[6]

HLA-F

The Major Histocompatibility Complex (MHC) is a group of cell surface proteins that in humans is also called the Human Leukocyte Antigen (HLA) complex. These proteins are encoded by a cluster of genes known as the HLA locus. The HLA locus occupies a ~ 3Mbp stretch that is located on the short arm of chromosome 6, specifically on 6p21.1-21.3. ^[7] The MHC proteins are classified into three main categories, namely class I, II, and III. There are over 140 genes within the HLA locus and they are often called HLA genes. ^{[8] [9]} HLA-A , B, and C are the classical class I genes and HLA-E, F and G are the nonclassical class I genes. ^{[10] [4]} The protein encoded from the gene HLA-F was originally isolated from the human lymphoblastoid cell line 721. ^[11]

Gene

The HLA-F gene is located on the short arm of chromosome 6, telomeric to the HLA-A locus. ^[10] HLA-F has little allelic polymorphism ^[8] and is highly conserved in other primates. ^[12] HLA-F appears to be a recombinant between two multigene families, one that comprises conserved sequences found in all class I proteins (single transmembrane span) and another distinct family of genes with a conserved 3’ UTR. Many of these genes are highly transcribed and differentially expressed. ^[4] The heavy chain gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, the putative peptide binding sites, exon 4 encodes the alpha3 domain, exon 5 and 6 encode the transmembrane region and exons 7 and 8 the cytoplasmic tail. However, exons 7 and 8 (the cytoplasmic tail) are not translated due to an in-frame translation termination codon in exon 6. ^[5]

Protein

The HLA-F protein is a ~40-41 kDa molecule with conserved domains. ^[13] Exon 7 is absent from the mRNA of HLA-F. ^{[4] [14]} The absence of this exon produces a modification in the cytoplasmic tail of the protein making it shorter relative to classical HLA class-I proteins. ^[4] The cytoplasmic tail helps HLA-F exit the endoplasmic reticulum, ^[15] and that function is primarily done by the amino acid valine found at the C-terminal end of the tail. ^{[15] [16]}

Structure

The structure of HLA-F is similar to that of the other HLA class I genes, which consist of eight exons.  Of the key residues likely to form from the floor of the groove, position 97 is a glycine whose residue is a single proton, whereas in most class Ia structures it is a charged residue and in HLA-E, it is a bulky hydrophobic tryptophan. If the HLA-F groove binds to a peptide, then the glycine residue will create space in the mid-portion of the groove which might allow larger side chains to fit and be accommodated . This nonclassical class I gene also has two histidine residues (His 114-His116) close together in the C-terminal groove floor, mirroring His-9-His99 in HLA-E. Tyr 7, Tyr 59, Tyr 159 and Tyr 171, which are typically involved in the hydrogen-bonding network to the peptide N-terminal residues, are conserved. ^[17]

The possible pocket regions of HLA-F include a situation where the A pocket is hydrophobic and similar to that of HLA-E, and pocket B retains Met 45 and Ala 67, which also characterize the HLA-E pocket and are likely to be hydrophobic and large. The C-pocket, however, differs significantly from that of the HLA-E with similarities to the C pocket of HLA-B8. In the D pocket region of this protein, the Asn 99 may favor a charged residue, but the other residues in this pocket, including phenylalanine make predictions hard to make. However, the F-pocket of HLA-F appears well conserved with HLA-E and the other class Ia molecules and likely favors an aliphatic group, such as leucine. ^{[17] [18]}

Expression

Classic HLA class I molecules interact with HLA-F through their heavy chain. ^[16] However, HLA class I molecules only interact with HLA-F when they are in the form of an open conformer (free of peptide). Thus, HLA-F is expressed independently of bound peptide. ^{[16] [19]}

Intracellular expression

HLA-F is expressed intracellularly in peripheral blood lymphocytes (PBL), resting lymphocyte cells (B, T, NK, and monocytes), tonsils, spleen, thymus, bladder, brain, colon, kidney, liver, lymphoblast, T cell leukemia, choriocarcinoma, and carcinoma. ^{[13] [20] [21]}

Extracellular expression

HLA-F is expressed on the cell surface of activated lymphocytes, HeLa cells, EBV-transformed lymphoblastoid cells, and in some activated monocyte cell lines. ^{[15] [20]} The surface expression of HLA-F coincides with the activated immune response since HLA-F is mostly found on the surface of stimulated T memory cells but not on circulating regulatory T cells. ^[22]

Expression during pregnancy

In the first trimester, HLA-F is weakly expressed in the trophoblastic elements residing outside the villi (extravillous trophoblast cells). Its expression increases and translocated onto the cell surface during the second trimester, coinciding with fetal growth which, in context, suggests it plays a role in development. ^[23]

Interaction with NK cells

HLA-F can be expressed in two ways on the cell surface: with  β2m and a peptide as a complex of HLA-F heavy chain  or without the peptide and  β2m as an open conformer with just the heavy chain. It can transport from the endoplasmic reticulum partially with the aid of tapasin, independent from the TAP protein complex, typically associated with antigen processing and transportation. Open conformer (OC) HLA-Fs can form homodimers and heterodimers with distinct HLA class I OCs, which may suggest they are involved in cross-presentation of extracellular antigens. ^[24]

 HLA OCs are able to bind to other receptors than the HLA complex with the β2m and peptide, most relevant to the diverse function of HLA-F. These receptors include binding inhibitory and activating immune receptors primarily expressed in natural killer (NK) cells, but also includes other immune cells. To do this, HLA OCs bind to the activating receptor KIR3DS1 and inhibitory receptor killer receptors 3DL1 and 3dL2. ^[18]

 Recent studies further suggest that HLA-F also presents long peptides (7 to more than 30 amino acids) to T cell receptors. They are able to do this because of an amino acid substitution in position 62 that forms an open-ended groove with N-terminal extensions. It is still not known if there may be consequences for this in the immune regulation at the feto-maternal contact zone. ^[24]

Transcriptional regulation of HLA-F

In the promoter of HLA-F, both studied regulatory modules display homology to the classical MHC class I genes. HLA-F has a conserved κB1 site enhancer bound by NF- κB, but the HLA-F gene is not induced by NF- κB without flanking regulatory sequences (such as IRSE) that provide a helper function. The IRSE in HLA-F is homologous to other classical MHC class I genes.  INF- γ also induces HLA-F with its IRSE (IFN-stimulated response element). Further, it is also induced by CIITA, a transcriptional coactivator that regulates the transcription of MHC class II genes. ^[25]

Function

HLA-F belongs to the non-classical HLA class I heavy chain paralogues. Compared to classical HLA class I molecules, it exhibits very few polymorphisms. This class I molecule mainly exists as a heterodimer associated with the invariant light chain β-2 microglobulin.

HLA-F is currently the most enigmatic of the HLA molecules. Hence, its precise functions still remain to be resolved. Though, in contrast to other HLA molecules, it mainly resides intracellularly and rarely reaches the cell surface, e.g. upon activation of NK, B and T cells. Unlike classical HLA class I molecules, which possess ten highly conserved amino acids responsible for antigen recognition, HLA-F only has 5, suggesting a biological function different from peptide presentation. Upon immune cell activation, HLA-F binds free forms of HLA class I molecules and reaches the cell surface as heterodimer. In this way HLA-F stabilizes HLA class I molecules that haven't yet bound peptides, thereby acting as a chaperone and transporting the free HLA class I to, on, and from the cell surface. ^[26]

Association with specialized ligands

HLA-F has been observed only in a subset of cell membranes, mostly B cells and activated lymphocytes. ^[23] As a result, it has been suggested that its role involves association with specialized ligands that become available in the cell membrane of activated cells. ^[13] For example, HLA-F can act as a peptide binding of ILT2 and ILT4. ^{[21] [6]} HLA-F can associate with TAP (transporter associated with antigen processing) and with the multimeric complex involved in peptide loading. ^{[13] [21] [20] [22]}

Maternal immunity tolerance

It has been observed that all three non-classical HLA class I proteins are expressed in placental trophoblasts in contact with maternal immune cells. ^[8] This suggests that these proteins collaborate in the immune response and that HLA-F plays a fundamental role in both normal and maternal immune response. ^[8] HLA-F is also expressed in decidual extravillous trophoblasts. ^[23] During pregnancy, HLA-F interacts with T reg cells and extravillous trophoblasts mediating maternal tolerance to the fetus. ^[22]

Intermolecular communication

During the interaction between HLA-F and the heavy chain (HC) of HLA class I molecules in activated lymphocytes, HLA-F plays a role as a chaperone, escorting HLA class I HC to the cell surface and stabilizing its expression in the absence of peptide. ^[16] HLA-F binds most allelic forms of HLA class I open conformers, but it does not bind peptide complexes. ^[19]

The expression patterns of HLA-F in T cells suggest that HLA-F is involved in the communication pathway between T reg and activated T cells, where HLA-F signals that the immune response has been activated. During this communication, either HLA-F invokes secretion of inhibitory cytokines by the regulatory T cells or it provides a simple inhibitory signal to the regulatory T cells, allowing a normal immune response to proceed. ^[22]

Exogenous antigen cross-presentation

Viral proteins and other exogenous antigens decrease surface HLA-F expression because the exogenous proteins interact with HLA class I molecules at the same sites where HLA-F interacts, producing crosslinking. The exogenous proteins trigger an internal co-localization of both HLA-F and HLA class I molecules. ^[19] Exogenous proteins with higher affinity will interact more readily with HLA class I molecules triggering a dissociation of HLA class I/HLA-F, thereby reducing the surface levels of HLA-F. ^[19] HLA-F interacts with the open conformer (OC) of HLA class I and they function together in cross-presentation of exogenous antigen. Exogenous antigen binds to a structure on the surface of activated cells; this structure is composed of HLA class I open conformer and HLA-F; the peptide-binding point of contact is a specific HLA class I epitope on the exogenous antigen. ^[19]

Ligand during inflammatory response

The complex HLA-F/HLA class I OC has two distinct roles that are central to the inflammatory response: first, it is a ligand for KIR receptors and can both activate and inhibit KIR; second, it is involved in cross-presentation of exogenous antigen. ^{[27] [28] [18]}

The complex HLA-F/HLA class-I OC is a ligand for a subset of KIR (Killer-cell immunoglobulin-like receptor) receptors. ^[27] Specifically, it was demonstrated that HLA-F interacts physically and functionally with three KIR receptors: KIR3DL2, KIR2DS4, and KIR3DS1, particularly during the inflammatory response. ^{[27] [28] [18]} KIR directly interacts with both HLA-F and HLA class-I individually (i.e. no dimerization between HLA-F and HLA class-I is necessary).

Disease association

HLA-F has been linked to several diseases (Table). For cancer and tumors, HLA-F expression has been found to be enhanced in gastric adenocarcinoma, ^[29] breast cancer, ^[30] esophageal carcinoma, ^[31] lung cancer, ^[32] hepatocellular carcinoma, ^[33] and neuroblastoma. ^[34] HLA-F has also been associated with susceptibility to several diseases: hepatitis B, ^[35] Systemic Lupus Erythematosus, ^[36] and Type 1 diabetes (T1D). ^[37]

Disease associations

disease	reference
gastric adenocarcinoma	[29]
breast cancer	[30]
esophageal carcinoma	[31]
lung cancer	[32]
hepatocellular carcinoma	[33]
neuroblastoma	[34]
hepatitis B	[35]
Systemic Lupus Erythematosus	[36]
Type 1 Diabetes	[37]

References

1. ENSG00000237508, ENSG00000234487, ENSG00000206509, ENSG00000137403, ENSG00000235220, ENSG00000204642 GRCh38: Ensembl release 89: ENSG00000229698, ENSG00000237508, ENSG00000234487, ENSG00000206509, ENSG00000137403, ENSG00000235220, ENSG00000204642 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Geraghty DE, Wei XH, Orr HT, Koller BH (January 1990). "Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element". The Journal of Experimental Medicine. 171 (1): 1–18. doi:10.1084/jem.171.1.1. PMC   2187653 . PMID   1688605.
5. "Entrez Gene: HLA-F major histocompatibility complex, class I, F".
6. Allan DS, Lepin EJ, Braud VM, O'Callaghan CA, McMichael AJ (October 2002). "Tetrameric complexes of HLA-E, HLA-F, and HLA-G". Journal of Immunological Methods. 268 (1): 43–50. doi:10.1016/s0022-1759(02)00199-0. PMID   12213342.
7. Krebs J, Goldstein E, Kilpatrick S (2014). "Chapter 18: Somatic recombination and hypermutation in the immune system". Lewin's GENES XI. USA: Jones & Bartlett Learning. pp. 459–99. ISBN   978-1-4496-5985-1.
8. Pyo CW, Williams LM, Moore Y, Hyodo H, Li SS, Zhao LP, et al. (May 2006). "HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes". Immunogenetics. 58 (4): 241–251. doi:10.1007/s00251-005-0076-z. PMID   16570139. S2CID   22308414.
9. Smith WP, Vu Q, Li SS, Hansen JA, Zhao LP, Geraghty DE (May 2006). "Toward understanding MHC disease associations: partial resequencing of 46 distinct HLA haplotypes". Genomics. 87 (5): 561–571. doi: 10.1016/j.ygeno.2005.11.020 . PMID   16434165.
10. Koller BH, Geraghty DE, DeMars R, Duvick L, Rich SS, Orr HT (February 1989). "Chromosomal organization of the human major histocompatibility complex class I gene family". The Journal of Experimental Medicine. 169 (2): 469–480. doi:10.1084/jem.169.2.469. PMC   2189218 . PMID   2562983.
11. Geraghty DE, Koller BH, Orr HT (December 1987). "A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment". Proceedings of the National Academy of Sciences of the United States of America. 84 (24): 9145–9149. Bibcode:1987PNAS...84.9145G. doi: 10.1073/pnas.84.24.9145 . PMC   299709 . PMID   3480534.
12. Daza-Vamenta R, Glusman G, Rowen L, Guthrie B, Geraghty DE (August 2004). "Genetic divergence of the rhesus macaque major histocompatibility complex". Genome Research. 14 (8): 1501–1515. doi:10.1101/gr.2134504. PMC   509259 . PMID   15289473.
13. Wainwright SD, Biro PA, Holmes CH (January 2000). "HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern". Journal of Immunology. 164 (1): 319–328. doi: 10.4049/jimmunol.164.1.319 . PMID   10605026.
14. O'Callaghan CA, Bell JI (June 1998). "Structure and function of the human MHC class Ib molecules HLA-E, HLA-F and HLA-G". Immunological Reviews. 163: 129–138. doi:10.1111/j.1600-065x.1998.tb01192.x. PMID   9700506. S2CID   6160579.
15. Boyle LH, Gillingham AK, Munro S, Trowsdale J (June 2006). "Selective export of HLA-F by its cytoplasmic tail". Journal of Immunology. 176 (11): 6464–6472. doi: 10.4049/jimmunol.176.11.6464 . PMID   16709803.
16. Goodridge JP, Burian A, Lee N, Geraghty DE (June 2010). "HLA-F complex without peptide binds to MHC class I protein in the open conformer form". Journal of Immunology. 184 (11): 6199–6208. doi:10.4049/jimmunol.1000078. PMC   3777411 . PMID   20483783.
17. Sim MJ, Sun PD (June 2017). "HLA-F: A New Kid Licensed for Peptide Presentation". Immunity. 46 (6): 972–974. doi: 10.1016/j.immuni.2017.06.004 . PMID   28636965.
18. Garcia-Beltran WF, Hölzemer A, Martrus G, Chung AW, Pacheco Y, Simoneau CR, et al. (September 2016). "Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1". Nature Immunology. 17 (9): 1067–1074. doi:10.1038/ni.3513. PMC   4992421 . PMID   27455421.
19. Goodridge JP, Lee N, Burian A, Pyo CW, Tykodi SS, Warren EH, et al. (August 2013). "HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway". Journal of Immunology. 191 (4): 1567–1577. doi:10.4049/jimmunol.1300080. PMC   3732835 . PMID   23851683.
20. Lee N, Geraghty DE (November 2003). "HLA-F surface expression on B cell and monocyte cell lines is partially independent from tapasin and completely independent from TAP". Journal of Immunology. 171 (10): 5264–5271. doi: 10.4049/jimmunol.171.10.5264 . PMID   14607927.
21. Lepin EJ, Bastin JM, Allan DS, Roncador G, Braud VM, Mason DY, et al. (December 2000). "Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors". European Journal of Immunology. 30 (12): 3552–3561. doi:10.1002/1521-4141(200012)30:12<3552::AID-IMMU3552>3.0.CO;2-L. PMID   11169396. S2CID   42462661.
22. Lee N, Ishitani A, Geraghty DE (August 2010). "HLA-F is a surface marker on activated lymphocytes". European Journal of Immunology. 40 (8): 2308–2318. doi:10.1002/eji.201040348. PMC   3867582 . PMID   20865824.
23. Ishitani A, Sageshima N, Lee N, Dorofeeva N, Hatake K, Marquardt H, Geraghty DE (August 2003). "Protein expression and peptide binding suggest unique and interacting functional roles for HLA-E, F, and G in maternal-placental immune recognition". Journal of Immunology. 171 (3): 1376–1384. doi: 10.4049/jimmunol.171.3.1376 . PMID   12874228.
24. Burian A, Wang KL, Finton KA, Lee N, Ishitani A, Strong RK, Geraghty DE (2016-09-20). Allen RL (ed.). "HLA-F and MHC-I Open Conformers Bind Natural Killer Cell Ig-Like Receptor KIR3DS1". PLOS ONE. 11 (9): e0163297. Bibcode:2016PLoSO..1163297B. doi: 10.1371/journal.pone.0163297 . PMC   5029895 . PMID   27649529.
25. Jordier F, Gras D, De Grandis M, D'Journo XB, Thomas PA, Chanez P, et al. (2020). "HLA-H: Transcriptional Activity and HLA-E Mobilization". Frontiers in Immunology. 10: 2986. doi: 10.3389/fimmu.2019.02986 . PMC   6978722 . PMID   32010122.
26. Persson G, Jørgensen N, Nilsson LL, Andersen LH, Hviid TV (April 2020). "A role for both HLA-F and HLA-G in reproduction and during pregnancy?". Human Immunology. HLA-G Special Issue. 81 (4): 127–133. doi:10.1016/j.humimm.2019.09.006. PMID   31558330. S2CID   203568247.
27. Goodridge JP, Burian A, Lee N, Geraghty DE (October 2013). "HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors". Journal of Immunology. 191 (7): 3553–3562. doi:10.4049/jimmunol.1300081. PMC   3780715 . PMID   24018270.
28. Burian A, Wang KL, Finton KA, Lee N, Ishitani A, Strong RK, Geraghty DE (2016-09-20). "HLA-F and MHC-I Open Conformers Bind Natural Killer Cell Ig-Like Receptor KIR3DS1". PLOS ONE. 11 (9): e0163297. Bibcode:2016PLoSO..1163297B. doi: 10.1371/journal.pone.0163297 . PMC   5029895 . PMID   27649529.
29. Ishigami S, Arigami T, Okumura H, Uchikado Y, Kita Y, Kurahara H, et al. (April 2015). "Human leukocyte antigen (HLA)-E and HLA-F expression in gastric cancer". Anticancer Research. 35 (4): 2279–2285. PMID   25862890.
30. Harada A, Ishigami S, Kijima Y, Nakajo A, Arigami T, Kurahara H, et al. (November 2015). "Clinical implication of human leukocyte antigen (HLA)-F expression in breast cancer". Pathology International. 65 (11): 569–574. doi: 10.1111/pin.12343 . PMID   26332651.
31. Zhang X, Lin A, Zhang JG, Bao WG, Xu DP, Ruan YY, Yan WH (January 2013). "Alteration of HLA-F and HLA I antigen expression in the tumor is associated with survival in patients with esophageal squamous cell carcinoma". International Journal of Cancer. 132 (1): 82–89. doi:10.1002/ijc.27621. PMID   22544725. S2CID   23526646.
32. Lin A, Zhang X, Ruan YY, Wang Q, Zhou WJ, Yan WH (December 2011). "HLA-F expression is a prognostic factor in patients with non-small-cell lung cancer". Lung Cancer. 74 (3): 504–509. doi:10.1016/j.lungcan.2011.04.006. PMID   21561677.
33. Xu Y, Han H, Zhang F, Lv S, Li Z, Fang Z (January 2015). "Lesion human leukocyte antigen-F expression is associated with a poor prognosis in patients with hepatocellular carcinoma". Oncology Letters. 9 (1): 300–304. doi:10.3892/ol.2014.2686. PMC   4246689 . PMID   25435979.
34. Morandi F, Cangemi G, Barco S, Amoroso L, Giuliano M, Gigliotti AR, et al. (2013-11-21). "Plasma levels of soluble HLA-E and HLA-F at diagnosis may predict overall survival of neuroblastoma patients". BioMed Research International. 2013: 956878. doi: 10.1155/2013/956878 . PMC   3856218 . PMID   24350297.
35. Zhang J, Pan L, Chen L, Feng X, Zhou L, Zheng S (March 2012). "Non-classical MHC-Ι genes in chronic hepatitis B and hepatocellular carcinoma". Immunogenetics. 64 (3): 251–258. doi:10.1007/s00251-011-0580-2. PMID   22015712. S2CID   14765632.
36. Jucaud V, Ravindranath MH, Terasaki PI, Morales-Buenrostro LE, Hiepe F, Rose T, Biesen R (March 2016). "Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies". Clinical and Experimental Immunology. 183 (3): 326–340. doi:10.1111/cei.12724. PMC   4750595 . PMID   26440212.
37. Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, et al. (November 2016). "Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes". Diabetologia. 59 (11): 2448–2458. doi:10.1007/s00125-016-4067-4. PMC   5042874 . PMID   27506584.

Further reading

• Geyer M, Fackler OT, Peterlin BM (July 2001). "Structure--function relationships in HIV-1 Nef". EMBO Reports. 2 (7): 580–585. doi:10.1093/embo-reports/kve141. PMC   1083955 . PMID   11463741.
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (April 2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". Journal of Biosciences. 28 (3): 323–335. doi:10.1007/BF02970151. PMID   12734410. S2CID   33749514.
• Bénichou S, Benmerah A (January 2003). "[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]". Médecine/Sciences. 19 (1): 100–106. doi: 10.1051/medsci/2003191100 . PMID   12836198.
• Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E (February 2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm". Current Protein & Peptide Science. 5 (1): 1–8. doi:10.2174/1389203043486955. PMID   14965316.
• Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (April 2004). "HIV/SIV escape from immune surveillance: focus on Nef". Current HIV Research. 2 (2): 141–151. doi:10.2174/1570162043484924. PMID   15078178.
• Joseph AM, Kumar M, Mitra D (January 2005). "Nef: "necessary and enforcing factor" in HIV infection". Current HIV Research. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID   15638726.
• Anderson JL, Hope TJ (April 2004). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS Reports. 1 (1): 47–53. doi:10.1007/s11904-004-0007-x. PMID   16091223. S2CID   34731265.
• Kozlowski S, Corr M, Takeshita T, Boyd LF, Pendleton CD, Germain RN, et al. (June 1992). "Serum angiotensin-1 converting enzyme activity processes a human immunodeficiency virus 1 gp160 peptide for presentation by major histocompatibility complex class I molecules". The Journal of Experimental Medicine. 175 (6): 1417–1422. doi:10.1084/jem.175.6.1417. PMC   2119225 . PMID   1316930.
• Lury D, Epstein H, Holmes N (1991). "The human class I MHC gene HLA-F is expressed in lymphocytes". International Immunology. 2 (6): 531–537. doi:10.1093/intimm/2.6.531. PMID   1707659.
• Takahashi H, Merli S, Putney SD, Houghten R, Moss B, Germain RN, Berzofsky JA (October 1989). "A single amino acid interchange yields reciprocal CTL specificities for HIV-1 gp160". Science. 246 (4926): 118–121. Bibcode:1989Sci...246..118T. doi:10.1126/science.2789433. PMID   2789433.
• Dianzani U, Bragardo M, Buonfiglio D, Redoglia V, Funaro A, Portoles P, et al. (May 1995). "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". European Journal of Immunology. 25 (5): 1306–1311. doi:10.1002/eji.1830250526. PMID   7539755. S2CID   37717142.
• Howcroft TK, Palmer LA, Brown J, Rellahan B, Kashanchi F, Brady JN, Singer DS (July 1995). "HIV Tat represses transcription through Sp1-like elements in the basal promoter". Immunity. 3 (1): 127–138. doi: 10.1016/1074-7613(95)90165-5 . PMID   7621073.
• Chen YH, Böck G, Vornhagen R, Steindl F, Katinger H, Dierich MP (July 1994). "HIV-1 gp41 enhances major histocompatibility complex class I and ICAM-1 expression on H9 and U937 cells". International Archives of Allergy and Immunology. 104 (3): 227–231. doi:10.1159/000236670. PMID   7913356.
• Chen YH, Böck G, Vornhagen R, Steindl F, Katinger H, Dierich MP (September 1994). "HIV-1 gp41 binding proteins and antibodies to gp41 could inhibit enhancement of human Raji cell MHC class I and II expression by gp41". Molecular Immunology. 31 (13): 977–982. doi:10.1016/0161-5890(94)90092-2. PMID   8084338.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Howcroft TK, Strebel K, Martin MA, Singer DS (May 1993). "Repression of MHC class I gene promoter activity by two-exon Tat of HIV". Science. 260 (5112): 1320–1322. Bibcode:1993Sci...260.1320H. doi:10.1126/science.8493575. PMID   8493575.
• Gasparini P, Borgato L, Piperno A, Girelli D, Olivieri O, Gottardi E, et al. (May 1993). "Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F". Human Molecular Genetics. 2 (5): 571–576. doi:10.1093/hmg/2.5.571. PMID   8518796.
• Schwartz O, Maréchal V, Le Gall S, Lemonnier F, Heard JM (March 1996). "Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein". Nature Medicine. 2 (3): 338–342. doi:10.1038/nm0396-338. PMID   8612235. S2CID   7461342.
• Alexander-Miller MA, Parker KC, Tsukui T, Pendleton CD, Coligan JE, Berzofsky JA (May 1996). "Molecular analysis of presentation by HLA-A2.1 of a promiscuously binding V3 loop peptide from the HIV-envelope protein to human cytotoxic T lymphocytes". International Immunology. 8 (5): 641–649. doi: 10.1093/intimm/8.5.641 . PMID   8671651.