Evidence that HLA-G is the functional homolog of mouse Qa-2, the Ped gene product.
Qa-2, a murine class Ib major histocompatibility complex (MHC) molecule, is a possible functional homolog of human leukocyte antigen G (HLA-G). Both molecules have been implicated in immunoregulation and embryonic development and both occur in membrane-bound and soluble isoforms that arise by alternative splicing. Soluble splice variants have been implicated in the reproductive functions of HLA-G. While soluble variants of Qa-2 have been previously detected in T lymphocytes, we now demonstrate the presence of mRNA for one of the two known soluble forms of Qa-2 in eight-cell embryos and in blastocysts. Qa-2 is glycosylphosphatidylinositol (GPI) linked in the outer leaflet of the cell membrane and is found in lipid raft microdomains where other raft-associated proteins transduce signals into the cell. In contrast, HLA-G has a truncated six amino acid cytoplasmic tail. By fluorescence co-localization in JEG-3 cells, using fluorescent cholera toxin beta subunit (a lipid raft marker) and anti-HLA-G antibody, we have demonstrated that membrane-bound HLA-G also localizes to lipid rafts, consistent with functional homology between the two molecules. Finally, our experiments in which we have purified Qa-2 and transferred it via a process known as protein painting to Qa-2 negative cells represent a model for potential therapy involving HLA-G.
Comiskey
Martina
M
Department of Biology, Northeastern University, Boston, MA 02115, USA.
Goldstein
Carmit Y
CY
De Fazio
Sally R
SR
Mammolenti
Michele
M
Newmark
Judith A
JA
Warner
Carol M
CM
D000818:Animals; D001755:Blastocyst / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D006801:Humans; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011247:Pregnancy; D012313:RNA / Q000302:isolation & purification; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D017261:Glycosylphosphatidylinositols; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D012313:RNA