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

No evidence was found of physical association between HAFP and phytomitogens or antihuman thymocyte antiserum. In addition, 20 to 40 fold increases in mitogen dose did not reverse the inhibition of lymphocyte transformation by a constant dose of HAFP. The presence of HAFP did not interfere with the attachment of 125I-labelled phytohaemagglutinin to the lymphocyte surface. When analysed by 2-dimensional crossed immunoelectrophoresis, HAFP isolated from the body fluids of hepatoma patients displayed electrophoretic heterogeneity, and demonstrated three charged species of HAFP. The potency of hepatoma-HAFP isolates in inhibiting lymphocyte transformation was correlated with the proportions of these three species in different fractions obtained after passage over carboxymethyl-cellulose. The fraction enriched in the most electronegative species was the most potent. 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 HAPF 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. (author)