HLA-G remains a mystery

In this brief summary, we argue that many widely held beliefs about HLA-G a re questionable. Recent research has led to a re-evaluation of many of the characteristics that were thought to make HLA-G unusual among the MHC class I molecules. First, contrary to reports suggesting that the gene encoding HLA-G exhibits marked polymorphism in some human populations, recent data h ave shown that the HLA-G gene has comparatively little polymorphism-a featu re that might allow it to be expressed in the placenta without causing reje ction by the maternal immune system. Second, although truncated forms of HL A-G are generated in the placenta, most of them are unlikely to have signif icant biological effects as they do not reach the cell surface. Third, the hypothesis that a major role of HLA-G is to prevent attack of the placenta by maternal natural killer cells is now the subject of renewed scrutiny. Fi nally, there is little evidence that the induction of expression of HLA-G i s a major mechanism by which tumor cells avoid immune attack. HLA-G has onc e again become as mysterious as when it was discovered: an MHC class I mole cule expressed at a challengingly extraordinary site-the immunologically un easy interface between mother and fetus.