IDENTIFICATION OF A THYMIC EPITHELIAL-CELL SUBSET SHARING EXPRESSION OF THE CLASS IB HLA-G MOLECULE WITH FETAL TROPHOBLASTS

HLA-G is the only class I determinant of the major histocompatibility complex (MHC) expressed by the trophoblasts, the fetal cells invading the maternal decidua during pregnancy. A unique feature of this noncla ssical HLA molecule is its low polymorphism, a property that has been postulated to play an important role in preventing local activation of maternal alloreactive T and natural killer cells against the fetus. Y et, the mechanisms by which fetal HLA-G can be recognized as a self-MH C molecule by the maternal immune system remain unclear. Here we repor t the novel observation that HLA-G is expressed in the human thymus. E xpression is targeted to the cell surface of thymic medullary and subc apsular epithelium. Thymic epithelial cell lines were generated and sh own to express three alternatively spliced HLA-G transcripts, previous ly identified in human trophoblasts. Sequencing of HLA-G1 transcripts revealed a few nucleotide changes resulting in amino acid substitution s, all clustered within exon 3 of HLA-G, encoding for the alpha 2 doma in of the molecule. Our findings raise the possibility that maternal u nresponsiveness to HLA-G-expressing fetal tissues may be shaped in the thymus by a previously unrecognized central presentation of this MHC molecule on the medullary epithelium.