ELSEVIER zyxwvutsrqpo BRIEF COMMUNICATION zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Evidence for the Presence of the Alternatively Spliced HLA-G mRNA Forms in Human M ononuclear Cells from Peripheral Blood and Umbilical Cord Blood Marek Kirsaenbaum, Philippe Moreau, Magali Teyssier, Catherine Lafon, Eliane Jean Dausset, and Edgardo Carosella Gluckman, zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO ABSTRACT: The HLA-G monomorphic, nonclassic HLA class I gene encodes the molecule that is the only major histocompatibility complex antigen expressed on cytotrophoblasts of placenta. This restricted expression on fetal tissue that is in contact with maternal tissue suggests that HLA-G products may play a role in maternofetal tolerance. We previously have demonstrated in first- trimester human trophoblasts a new alternatively spliced form of HLA-G mRNA lacking exon 4 (HLA-G4) and weak expression of HLA-Gl copy mRNA in adult pe- ripheral blood lymphocytes. By using exon-specific ABBREVIATIONS CBMC cord blood mononuclear cell PBMC peripheral blood mononuclear cell NK natural killer INTRODUCTION HLA-G is one of the three nonclassic class I genes map- ping to the human major histocompatibility complex (for reviews, see Le Bouteiller El]. It presents a very limited polymorphism 12-4) and encodes a protein with a shortened cytoplasmic segment due to a translation stop codon in exon 6 15, 61. The HLA-G product was identified as an array of 37- to 39-kd isoforms and de- tected only in fetal cytotrophoblast and first-trimester zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC From the CEA-DSV-DPTE, Laboratoire d’lmmunoradiobiologie, H+itaISaint-Louis(M.K., P.M ., M .T., E.C.), A.P.-CEDlT(C.L.), Service de Greffe de Moelle Osseuse, H@ ital Saint-Louis (E.G.) and Fon- Ltion Jtzn DaussetXEPH (J.D.) Alidress repint requests to zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Dr. M. Kirszenbaum, Luboratoire d’lmmu- noradiobiologie, H@ ital Saint-Louis, Centre Hayem, I Avenue Claude Vellfaux, 75010 Paris, France. Reseiued (U) July 18, 1994; accepted January 12, 1995. HLA-G primers, we demonstrate in this work the pres- ence of three additional alternatively spliced forms of HLA-G mRNA in human peripheral mononuclear cells (HLA-G2, HLA-G3, and HLA-G4). In umbilical cord blood, HLA-G transcription was observed at very low level and only three alternatively spliced forms were de- tected (HLA-Gl, HLA-G2, and HLA-G3). In contrast, we did not revealed any HLA-G transcript in CD34 + fraction of cord blood cells. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR Human Immunology 43, 237- 241 (1995) PCR RT polymerase chain reaction reverse transcriptase liver 177. In contrast to classic class I genes, preferential expression in fetal tissues suggests that HLA-G may play a specific role in embryonic development and/or mater- nofetal immune response 181. Low amounts of HLA-G transcripts were reported in fetal eyes and thymus [9] but also in adult tissues like the anterior portion of eyes, which is recognized as an im- mune-privileged site IS], skin [lo], and human germ cells Ill]. Up to today, HLA-G antigen expression in these tissues has not been investigated. Using the sensi- tive hot-start polymerase chain reaction (PCR) technique rather than Northern blot, we have recently demon- strated the presence of a small level of HLA-G mRNA in peripheral blood lymphocytes 1121 although no HLA-G o-chain expression is detected [7]. HLA-G transcription is observed both in B and T cells without significant Human Immunology 43, 237- 24 1 (1995) 0 American Society for Histocompatibility and Immunogenetics, 1995 0198-8859l9569.50 SSDI 0198-8859(95)00008-R