Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence.

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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“…An ICS very similar to the human ICS has also been found in a murine H-2L gene (33). As can be seen in Fig.…”

Section: Hla-esupporting

confidence: 64%

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

187

102

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“…GAS site was first identified in guanylate binding protein (GBP) gene (Lew et al, 1991). IFN-γ c a u s e s transcrip-tional activation of GBP gene and a mutation in expression and regulation of this gene through specific DNA-binding proteins (Friedman et al, 1985, 1987, Shirayoshi et al, 1987, Sugita et al, 1987, D a v i d -Watine et al, 1990 (Figure 1, Table1). Mainly there are two enhancer like sequences, A (-203 to -161) and B (-120 to -61).…”

Section: Ifn Induced Protein Kinasesmentioning

confidence: 99%

Cytokine regulation of expression of class I MHC antigens

Raval

Puri²,

Rath³

et al. 1998

Exp Mol Med

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“…IFN-␥ induction of many class I genes is mediated, at least in part, by the ISRE located within the 5Ј promoter of the gene (17,18,35). CAT expression constructs consisting of 525 bp of the HLA-A2 promoter, either containing or lacking the ISRE, were transiently transfected into both K562 and Jurkat cells to determine whether IFN-␥ up-regulates expression of the HLA-A2 gene through the ISRE.…”

Section: A Transfected Full-length Hla-a2 Gene Is Inducible With Ifn-␥mentioning

confidence: 99%

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Snyder

Waring

Sheng

et al. 2001

The Journal of Immunology

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The expression of several MHC class I genes is up-regulated at the transcriptional level by IFN-γ. Posttranscriptional mechanisms also have been implicated, but not well characterized. To investigate the mechanism of IFN-γ stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines were transfected with reporter gene constructs driven by the HLA-A2 promoter. We have previously shown that the extended 525-bp HLA-A2 promoter alone, which includes a 5′ IFN-stimulated response element consensus sequence, is not sufficient for IFN-γ response in either K562 or Jurkat cells. In the current study, stable transfection of a genomic HLA-A2 gene construct, containing both 5′- and 3′-flanking sequences, resulted in stimulation of the gene by IFN-γ. Nuclear run-on assays revealed that, unlike other class I genes, IFN-γ stimulation of HLA-A mRNA accumulation occurs almost entirely through posttranscriptional mechanisms. RNA stability assays showed that the effect is not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the 3′ end was unaffected by IFN-γ treatment. Sequences that mediate the majority of IFN-γ induction of HLA-A2 mRNA reside in a 127-bp 3′-transcribed region of the gene. This region contains the terminal splice site, the usage of which is not affected by IFN-γ treatment. These results demonstrate a novel posttranscriptional mechanism of regulation of MHC class I genes by IFN-γ.

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Interferons increase transcription of a major histocompatibility class I gene via a 5' interferon consensus sequence.

Cited by 100 publications

References 40 publications

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

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

Cytokine regulation of expression of class I MHC antigens

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

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