title: Molecular cloning and immunologic characterization of a novel cDNA coding for progesterone-induced blocking factor.
abstract: Previous studies from our laboratory showed that the immunomodulatory effects of progesterone are mediated by a 34-kDa protein, named the progesterone-induced blocking factor (PIBF). Lymphocytes of women with threatened abortion fail to produce this factor. Via inducing a Th2 biased cytokine production and blocking of NK activity, PIBF prevents induced pregnancy loss in mice, suggesting that substitution therapy with PIBF could be useful as an alternative treatment of certain forms of recurrent spontaneous abortions. Our study was aimed at mapping the sequence and structure of PIBF coding cDNA and characterizing the encoded protein product. Screening of a human liver cDNA library revealed a 2765-bp clone with a 2271-bp open reading frame. The PIBF1 cDNA encodes a protein of 757 amino acid residues with an 89-kDa predicted molecular mass, which shows no significant amino acid sequence homology with any known protein. PIBF produced via recombinant technique is recognized by the Ab specific for the secreted lymphocyte PIBF Ab, and possesses the biological activities of the secreted lymphocyte PIBF. The full-length PIBF is associated with the nucleus, whereas secretion of shorter forms, such a 34-kDa protein is induced by activation of the cell. The 48-kDa N-terminal part of PIBF is biologically active, and the part of the molecule, responsible for modulating NK activity is encoded by exons 2-4. These data provide an initial step for exploiting the possible diagnostic and therapeutic potential of this immunomodulatory molecule.
authors.affiliation: Department of Medical Microbiology and Immunology, Pecs University Medical School, Pecs, Hungary.
authors.forename: Beata
authors.initials: B
authors.lastname: Polgar
authors.forename: Gyula
authors.initials: G
authors.lastname: Kispal
authors.forename: Margit
authors.initials: M
authors.lastname: Lachmann
authors.forename: Christian
authors.initials: C
authors.lastname: Paar
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.forename: Peter
authors.initials: P
authors.lastname: Csere
authors.forename: Eva
authors.initials: E
authors.lastname: Miko
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szereday
authors.forename: Peter
authors.initials: P
authors.lastname: Varga
authors.forename: Julia
authors.initials: J
authors.lastname: Szekeres-Bartho
authors.forename: Gabriella
authors.initials: G
authors.lastname: Paar
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D003001:Cloning, Molecular / Q000379:methods*; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D018076:DNA, Complementary / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D013491:Suppressor Factors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D018076:DNA, Complementary; D007106:Immune Sera; C110058:PIBF1 protein, human; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D013491:Suppressor Factors, Immunologic