A postsynthetic modification of human α-fetoprotein controls its immunosuppressive potency

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Abstract
In a previous study, 3 variants of human .alpha.-fetoprotein were demonstrated by crossed immunoelectrophoresis. In addition, the capacity of .alpha.-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro was correlated with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. In the experiments reported here, .alpha.-fetoprotein was isolated from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient and from a homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver .alpha.-fetoprotein were extremely potent, serum .alpha.-fetoprotein had intermediate potency and ascitic fluid .alpha.-fetoprotein was the least potent. Analysis of these isolates by crossed immunoelectrophoresis confirmed the correlation between the proportion of HAFP-3 and the immunosuppressive potency of each isolate. Analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least 6 molecular variants were apparent. The proportion of 1 of these variants, termed HAFP-3a, in each isolate was correlated with the immunosuppressive potency of the isolate. The sialic acid content of the various .alpha.-fetoprotein isolates did not vary significantly. A postsynthetic modification of .alpha.-fetoprotein occurs, probably after secretion, which reduces immunosuppresive potency by converting the active electronegative species to an inactive electropositive form. This modification probably involves a charged moiety other than sialic acid on the molecule.