Inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP): studies on the mode of HAFP action and the role of HAFP polymorphism.

In an effort to explain the mechanism of inhibition of human lymphocyte transformation by human alpha-foetoprotein (HAFP), we sought for, and failed to find, evidence of physical association between HAFP and phytomitogens or antihuman thymocyte antiserum. In addition, 20–40 fold increases in mitogen dose do not reverse the inhibition of lymphocyte transformation by a constant dose of HAFP. The presence of HAFP does not interfere with the attachment of I-labelled phytohaemagglutinin to the lymphocyte surface. When analyzed by 2-dimensional crossed immunoelectrophoresis, HAFP isolated from the body fluids of hepatoma patients displays electrophoretic heterogeneity, and demonstrates three charged species of HAFP designated as HAFP-1 (the most cathodal), HAFP-2, and HAFP-3 (the most anodal). The potency of hepatoma-HAFP isolates in inhibiting lymphocyte transformation can be positively correlated with the ratio HAFP-3:HAFP-1 in each preparation. Passage of hepatoma HAFP isolates over CM-cellulose allows the isolation of two distinct HAFP fractions, one at pH 4.95, and the other at pH 5.24. The pH 4.95 CM-cellulose isolate is enriched in the more electronegative HAFP species (HAFP-3) and is, on the average, two times more potent than the pH 5.24 CM-cellulose HAFP isolate. The latter, by comparison with native HAFP, is enriched in the more electropositive HAFP species (HAFP-1). The structural basis for the charge differences which govern the biological potency of HAFP as a modulator of lymphocyte responses is unknown, but it is independent of HAFP sialic acid content. Inhibition of lymphocyte transformation by HAFP cannot be explained by simple competition between the lymphocyte membrane and HAFP for the mitogen combining sites.