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Post-synthetic modification of human alpha-fetoprotein revealed by isoelectric focusing controls its immunosuppressive potency

Conference ·
OSTI ID:5374636

We have demonstrated 3 variants of human alpha-fetoprotein (HAFP) by crossed immunoelectrophoresis, and have correlated the capacity of HAFP isolates 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 HAFP from the serum, ascitic fluid, and saline extract of tumor from a single hepatoma patient, and from an homogenate of fetal livers. When tested for their capacity to inhibit human lymphocyte transformation in vitro, tumor and fetal liver HAFP were found to be extremely potent; serum HAFP had intermediate potency, and ascitic fluid HAFP was the least potent. Analysis of these HAFP 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 HAFP 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 one 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 HAFP isolates did not vary significantly. Our data suggest that a post-synthetic modification of HAFP occurs, which modulates its immunosuppressive potency.

Research Organization:
Chicago Univ., Ill. (USA). Dept. of Medicine; Franklin McLean Memorial Research Inst., Chicago, Ill. (USA)
Sponsoring Organization:
USDOE
OSTI ID:
5374636
Report Number(s):
CONF-770860-3
Country of Publication:
United States
Language:
English