Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
<h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET fa...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19223974/?tool=EBI |
| _version_ | 1819280443983265792 |
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| author | Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale |
| author_facet | Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale |
| author_sort | Robert A Eagle |
| collection | DOAJ |
| description | <h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised.<h4>Methodology/principal findings</h4>We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy.<h4>Conclusions/significance</h4>We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality. |
| first_indexed | 2024-12-24T00:43:53Z |
| format | Article |
| id | doaj.art-fc713ba0efb440538c1dc3d4584813bd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T00:43:53Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fc713ba0efb440538c1dc3d4584813bd2022-12-21T17:23:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0142e450310.1371/journal.pone.0004503Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.Robert A EagleGillian FlackAnthony WarfordJesús Martínez-BorraInsiya JafferjiJames A TraherneMaki OhashiLouise H BoyleAlexander D BarrowSophie Caillat-ZucmanNeil T YoungJohn Trowsdale<h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised.<h4>Methodology/principal findings</h4>We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy.<h4>Conclusions/significance</h4>We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19223974/?tool=EBI |
| spellingShingle | Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. PLoS ONE |
| title | Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. |
| title_full | Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. |
| title_fullStr | Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. |
| title_full_unstemmed | Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. |
| title_short | Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G. |
| title_sort | cellular expression trafficking and function of two isoforms of human ulbp5 raet1g |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19223974/?tool=EBI |
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