Abnormal in vitro function of a variant human transferrin.

Normal and variant transferrins have been isolated from the plasma of an individual heterozygous for the abnormal protein. The normal and variant proteins were separated, saturated with 59Fe, labelled with 125I and then compared in their interaction with PHA-stimulated human lymphocytes in vitro. At 4 degrees C the variant protein bound to the transferrin receptors on these cells with an association constant (6.25 +/- 2.53 X 10(7) l mol-1, mean +/- SD; n = 4) which was an order of magnitude lower than that of the normal diferric transferrin (6.31 +/- 1.82 X 10(8) l mol-1, mean +/- SD; n = 4). This low association constant was reflected in a much reduced rate of iron donation to the cells at 37 degrees C (22.2 +/- 8.3 pg/10(6) cells/h compared with 48.1 +/- 15.6 pg/10(6) cells/h). As the variant transferrin has both abnormal iron-binding properties (Evans et al, 1982) and an abnormal interaction with the transferrin receptor, it would appear that these two functions may be closely interdependent.