A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment.

Geraghty, Daniel E.; Koller, Beverly H.; Orr, Harry T.

doi:10.1073/pnas.84.24.9145

Cited by 465 publications

(267 citation statements)

References 31 publications

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“…The gene responsible for HH has been located on the short arm of chromosome 6, in linkage desequilibrium with the HLA-A locus (8,58), where several nonclassical MHC-I genes have been identified (59)(60)(61). While this paper was under submission, a novel MHC class I-like gene, termed HLA-H, was reported to be mutated in a large majority of HH patients (62).…”

Section: Molecular Nature Of the Defectmentioning

confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

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Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.

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Section: Molecular Nature Of the Defectmentioning

confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

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“…pregnancy | decidua | human | HCMV | cytotoxicity C onstitutive HLA-G expression in healthy tissue is restricted to fetal extravillous trophoblasts (EVT) that invade maternal decidual tissue during pregnancy (1)(2)(3). HLA-G acts mainly to prevent NK cell cytotoxicity (4-6) and T-cell cytotoxicity (7) and induce tolerance (8,9).…”

mentioning

confidence: 99%

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

Tilburgs

Evans

Crespo

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

155

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The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal–fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G–negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity.

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“…in the identification of two class I-related genes (9)(10)(11) . These genes have been sequenced and shown to encode intact HLA class I proteins distinct from the classical HLA-A, -B, and -C antigens.…”

mentioning

confidence: 99%

Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element.

Geraghty

Wei

Orr

et al. 1990

The Journal of Experimental Medicine

Self Cite

187

102

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We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than that of the classical transplantation antigens. The 3' untranslated region of the HLA-5.4 gene contains one member of a previously undescribed multigene family consisting of at least 30 members. Northern analysis showed that several of these sequences were transcribed, and the most ubiquitous transcript, a 600-nucleotide polyadenylated mRNA, was found in all tissues and cells examined. This sequence is conserved in the mouse genome, where a similar number of copies were found, and one of these sequences was also transcribed, yielding a 600-nucleotide mRNA. The characterization of this unique HLA class I gene and the demonstration of its tissue-specific expression have prompted us to propose that HLA-5.4 be designated HLA-F.

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A human major histocompatibility complex class I gene that encodes a protein with a shortened cytoplasmic segment.

Cited by 465 publications

References 31 publications

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

The HLA-G cycle provides for both NK tolerance and immunity at the maternal–fetal interface

Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element.

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