A postsynthetic modification of human alpha-fetoprotein controls its immunosuppressive potency.
In a previous study, we demonstrated three variants of human alphafetoprotein by crossed immunoelectrophoresis. In addition, we correlated the capacity of alpha-fetoprotein isolates from various hepatoma and fetal sources to suppress human lymphocyte transformation in vitro with the relative proportion of the electronegative variant, HAFP-3, present in each isolate. We have now isolated alpha-fetoprotein 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 alphafetoprotein were found to be extremely potent, serum alphafetoprotein 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. In addition, analysis of these isolates by isoelectric focusing in polyacrylamide gels containing 8 M urea revealed further evidence of microheterogeneity; at least six molecular variants were apparent. The proportion of one of these variants, termed HAFP-3a, in each isolate was correlated with the immunosupressive potency of the isolate. The sialic acid content of the various alpha-fetoprotein isolates did not vary significantly. Our data suggest that a postsynthetic modification of alphafetoprotein occurs, probably after secretion, which reduces immunosuppressive 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.
D006528:Carcinoma, Hepatocellular / Q000276:immunology; D005260:Female; D005333:Fetus; D014644:Genetic Variation; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D007165:Immunosuppression Therapy; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation; D008970:Molecular Weight; D011247:Pregnancy; D000509:alpha-Fetoproteins / Q000235:genetics
D000509:alpha-Fetoproteins