title: Quantified colocalization reveals heterotypic histocompatibility class I antigen associations on trophoblast cell membranes: relevance for human pregnancy.
abstract: Human placental syncytiotrophoblasts lack expression of most types of human leukocyte antigen (HLA) class I and class II molecules; this is thought to contribute to a successful pregnancy. However, the HLA class Ib antigens HLA-G, -E, and -F and the HLA class Ia antigen HLA-C are selectively expressed on extravillous trophoblast cells, and they are thought to play a major role in controlling feto-maternal tolerance. We have hypothesized that selective expression, coupled with the preferential physical association of pairs of HLA molecules, contribute to the function of HLA at the feto-maternal interface and the maternal recognition of the fetus. We have developed a unique analytical model that allows detection and quantification of the heterotypic physical associations of HLA class I molecules expressed on the membrane of human trophoblast choriocarcinoma cells, ACH-3P and JEG-3. Automated image analysis was used to estimate the degree of overlap of HLA molecules labeled with different fluorochromes. This approach yields an accurate measurement of the degree of colocalization. In both JEG-3 and ACH-3P cells, HLA-C, -E, and -G were detected on the cell membrane, while the expression of HLA-F was restricted to the cytoplasm. Progesterone treatment alone induced a significant increase in the expression level of the HLA-G/HLA-E association, suggesting that this heterotypic association is modulated by this hormone. Our data shows that the cell-surface HLA class I molecules HLA-G, -E, and -C colocalize with each other and have the potential to form preferential heterotypic associations.
authors.affiliation: School of Biological Sciences, University of Essex, Colchester, United Kingdom.
authors.forename: Asma
authors.initials: A
authors.lastname: Jabeen
authors.forename: José Maria
authors.initials: JM
authors.lastname: Miranda-Sayago
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Obara
authors.forename: Patrick Simon
authors.initials: PS
authors.lastname: Spencer
authors.forename: Gill Barbara
authors.initials: GB
authors.lastname: Dealtry
authors.forename: Soren
authors.initials: S
authors.lastname: Hayrabedyan
authors.forename: Valerie
authors.initials: V
authors.lastname: Shaikly
authors.forename: Pierre Philippe
authors.initials: PP
authors.lastname: Laissue
authors.forename: Nelson
authors.initials: N
authors.lastname: Fernández
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015236:HLA-C Antigens / Q000378:metabolism*; D059951:HLA-G Antigens / Q000737:chemistry / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000378:metabolism*; D054502:Histocompatibility, Maternal-Fetal; D006801:Humans; D006822:Hybrid Cells; D007091:Image Processing, Computer-Assisted; D018613:Microscopy, Confocal; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D021381:Protein Transport; D013499:Surface Properties; D014327:Trophoblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D000097625:HLA-E Antigens
chemical_list: D015236:HLA-C Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D011374:Progesterone; D000097625:HLA-E Antigens; C062341:HLA-F antigens
keywords: MHC class I; bioimaging; bioinformatics; immunology; implantation; pregnancy; progesterone; trophoblasts