The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/7/289/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 2, July 21, 1997 289-298

Article

Identification of a Thymic Epithelial Cell Subset Sharing Expression of the Class Ib HLA-G Molecule with Fetal Trophoblasts

Laura Crisa*, Michael T. McMaster{ddagger}, Jennifer K. Ishii*, Susan J. Fisher{ddagger}, and Daniel R. Salomon*

From the * Department of Molecular and Experimental Medicine and Immunology, The Scripps Research Institute, La Jolla, California 92037; and {ddagger} Department of Stomatology, University of California San Francisco, San Francisco, California 94143

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 nonclassical 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. Yet, the mechanisms by which fetal HLA-G can be recognized as a self-MHC molecule by the maternal immune system remain unclear. Here we report the novel observation that HLA-G is expressed in the human thymus. Expression is targeted to the cell surface of thymic medullary and subcapsular epithelium. Thymic epithelial cell lines were generated and shown to express three alternatively spliced HLA-G transcripts, previously identified in human trophoblasts. Sequencing of HLA-G1 transcripts revealed a few nucleotide changes resulting in amino acid substitutions, all clustered within exon 3 of HLA-G, encoding for the {alpha}2 domain of the molecule. Our findings raise the possibility that maternal unresponsiveness 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.

Address correspondence to Dr. Laura Crisa, Department of Molecular and Experimental Medicine - SBR5, The Scripps Research Institute, 10550 North Torrey Pines, La Jolla, CA 92037. Phone: 619-784-2023; FAX: 619-784-2243; E-mail: crisa{at}scripps.edu

L. Crisa was supported by a grant from the academic affairs section of the Scripps Clinic and Research Foundation. The confocal microscopy was performed at the National Center for Microscopy and Imaging Research supported by National Institutes of Health grant RR04050 to Dr. Mark Ellisman, whose expert advice was greatly appreciated.

This is manuscript No. 10398-MEM from the Scripps Research Institute.

1Abbreviations used in this paper: EpCAM, epithelial cell adhesion molecule; FSC, forward side scatter; mRNA, messenger RNA; RT-PCR, reverse transcriptase PCR.


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