LFA-1 p-chain synthesis and degradation in patients with leukocyte-adhesive proteins deficiency*
The defective membrane expression of the adhesive protein family (LFA-1, Mol and p150,93) on leukocytes from certain patients with recurrent bacterial infections was shown to be secondary to the absence of synthesis of mature p chain that is common to all three antigens . In all patients, studies of P-chain biosynthesis that lead to this conclusion were performed using the monoclonal anti8 chain antibody to isolate the P subunit. Since this antibody detects the mature form of @ chain only, the potential presence of a precursor or of an abnormal P chain in the patient's cells could not be tested. The availability of the polyclonal antibody to the purified P subunit allowed us to re-examine the biosynthesis of the LFA-1 subunits in 3 affected children. In all 3 patients, the absence of membrane expression of the LFA-1, CR3 and p150,95 proteins was confirmed. The LFA-1 a-chain precursor of 170 kDa was detected in the lysates of PHA blasts of two children, but was not detected in the third. The P-chain precursor of 85 kDa was isolated by the polyclonal anti-P chain antiserum from the cytoplasm of phytohemagglutinin and Epstein-Barr virus-induced blasts of one patient. The same antibody precipitated some peptides of smaller mol. wt. from the cell lysates of 2 other patients. These results suggest that in this disorder the membrane nonexpression of the adhesive proteins is probably due to the structural abnormality of p chain which, although synthesized, is rapidly degradated.