| Synthesis of beta(2)-microglobulin-free, disulphide-linked HLA-G5 homodimers in human placental villous cytotrophoblast cells. | |
| | |
MedLine Citation:
|
PMID: 17484767 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Human leucocyte antigen-G (HLA-G) is a natural immunosuppressant produced in human placentas that binds differently to the inhibitory leucocyte immunoglobulin-like receptors LILRB1 (ILT2) and LILRB2 (ILT4) according to its biochemical structure. To predict the binding functions of the HLA-G5 soluble isoform synthesized in placental villous cytotrophoblast (vCTB) cells, we investigated structural features of this protein. Biochemical and immunological studies showed that vCTB cell HLA-G5 heavy (H)-chain proteins are disulphide-bonded homodimers unassociated with beta(2)-microglobulin (beta2m) light-chain proteins. Although comparatively low levels of beta2m messenger RNA (mRNA) were identified by real-time reverse transcription-polymerase chain reaction, immunoprecipitation studies failed to detect beta2m protein even when specific mRNA was doubled by transduction of a lentivirus-beta2m complementary DNA into vCTB cells. No abnormalities were identified in the translational start codon of vCTB cell beta2m mRNA and differentiation into syncytium did not promote beta2m synthesis. The failure of vCTB cells to exhibit beta2m in vitro was paralleled by a lack of detectable beta2m in vCTB cells in vivo. Lack of the beta2m protein could be the result of low levels of beta2m transcripts or of as yet unidentified translational defects. Experiments with recombinant ectodomains of LILRB indicate that beta2m-free HLA-G binds strongly to LILRB2, a receptor that is expressed by macrophages. This potentially immunosuppressive cell type is abundant in the pregnant uterus. Thus, our findings are consistent with the postulate that the natural beta2m-free homodimeric form of HLA-G5 synthesized in primary vCTB cells could comprise a particularly effective tolerogenic molecule at the maternal-fetal interface. |
| | |
Authors:
|
Pedro J Morales; Judith L Pace; Jeralyn Sue Platt; Daudi K Langat; Joan S Hunt |
Related Documents
:
|
19041327 - Hdac2 deacetylates class ii transactivator and suppresses its activity in macrophages a... 8402937 - Cytokine production in first trimester chorionic villi: detection of mrnas and protein ... 15486347 - Nitric oxide mediates increased p-glycoprotein activity in interferon-{gamma}-stimulate... 15905497 - Cutting edge: generation of splenic cd8+ and cd8- dendritic cell equivalents in fms-lik... 22615357 - Nuclear export of single native mrna molecules observed by light sheet fluorescence mic... 12002677 - An atp-dependent step is required for the translocation of microinjected precursor mrna... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-05-02 |
Journal Detail:
|
Title: Immunology Volume: 122 ISSN: 0019-2805 ISO Abbreviation: Immunology Publication Date: 2007 Oct |
Date Detail:
|
Created Date: 2007-09-12 Completed Date: 2007-11-09 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0374672 Medline TA: Immunology Country: England |
Other Details:
|
Languages: eng Pagination: 179-88 Citation Subset: IM |
Affiliation:
|
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160-7400, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cells, Cultured Disulfides / metabolism Epidermal Growth Factor / pharmacology HLA Antigens / biosynthesis* Histocompatibility Antigens Class I / biosynthesis* Humans Immune Tolerance Lentivirus / genetics Placenta / immunology* Protein Biosynthesis RNA, Messenger / genetics Transduction, Genetic Trophoblasts / drug effects, immunology* beta 2-Microglobulin / biosynthesis, genetics |
| Grant Support | |
ID/Acronym/Agency:
|
P01 HD39878/HD/NICHD NIH HHS; P01 HD40984/HD/NICHD NIH HHS; P20 RR16475/RR/NCRR NIH HHS; U54 HD33994/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Disulfides; 0/HLA Antigens; 0/HLA-G antigen; 0/Histocompatibility Antigens Class I; 0/RNA, Messenger; 0/beta 2-Microglobulin; 62229-50-9/Epidermal Growth Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The effects of dietary lycopene supplementation on human seminal plasma.
Next Document: Dose-dependent modulation of CD8 and functional avidity as a result of peptide encounter.