The juxtaposition of maternal and fetal tissues in the hemochorial pla
centa has led to speculation that maternal recognition of fetal Ags pr
esent on trophoblasts might play an important role in reproductive bio
logy. We report here for the first time such recognition of trophoblas
ts by T lymphocyte hybridomas representative of certain cells present
in the maternal decidua. Trophoblast recognition is TCR dependent and
is mediated by members of the V gamma 1(+) subset of gamma delta T lym
phocytes, a population that we previously have shown to be associated
with heat shock protein-60 reactivity. Recognition occurred in experim
ents in which trophoblast clones or freshly prepared trophoblasts were
used and requires cell-cell interaction. Although the maternal-fetal
immune relationship typically has been cast in terms of an allograft,
the T cell recognition of trophoblasts as described herein is not MHC-
restricted, inasmuch as freshly prepared trophoblasts from beta(2)-mic
roglobulin-deficient mice were found to be stimulatory. Furthermore, t
he trophoblast ligand that mediates this recognition is probably a con
served mammalian molecule, because a human trophoblast cell line is al
so stimulatory. Our findings suggest a novel form of T cell recognitio
n, and may provide an enhanced understanding of the maternal-fetal imm
une relationship.