Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming gro
wthfactor-
![](/images/gifchars/beta2.gif)
(TGF-
![](/images/gifchars/beta2.gif)
) superfamily
whose increased expression is associated
with macrophage activation and
which is expressed highly in placenta as compared to other tissues. There are t
wo kno
wn allelic forms ofhuman MIC-1 due an amino acid substitution at position 6 of the mature protein. We have raised fourmonoclonal antibodies (MAbs) and one polyclonal antiserum to the mature protein region of human MIC-1and have used an extensive panel of MIC-1 relatives, mutants, and chimeras to map their epitopes. Noneof the MAbs
were able to cross-react
with either the murine homologue of MIC-1 or
with hTGF-
![](/images/gifchars/beta2.gif)
1, andall of the MAb epitopes
were conformation-dependent. A distinct cross-reactivity pattern
with the variousantigens
was observed for each of the monoclonal and polyclonal antibodies suggesting the presence ofat least five immunogenic regions on the MIC-1 surface. One of the MAbs is directed against the aminoterminus of the protein and can distinguish bet
ween the t
wo allelic forms of MIC-1. The epitopes for theother three MAbs
were located near the tips of the so-called "fingers" of the protein and appeared to bepartially overlapping as each involved amino acids in the region 24-37. In one case, it
was possible tomutate murine MIC-1 so that it could be recognized by one of the MAbs. Finally, the use of anothermutant in
which Cys 77
was replaced by serine enabled confirmation of the location of the MIC-1 interchaindisulfide bond.