Activation of human platelets by antibodies to thymocytes and beta 2-microglobulin. II. Effect of purified beta 2m on the platelet aggregating and lymphocytotoxic activities of HATG and SA beta 2mG.

Platelet aggregating (PAA) and lymphocytotoxic activities (LTA) of antibody preparations known to have immunosuppressive properties were studied in this work. In comparison to sheep anti-human beta-2-microglobulin globulin (SA beta 2mG), horse anti-human thymocyte globulin (HATG) was about twice as potent by weight in LTA than in PAA, suggesting that a considerable portion of antibodies in HATG had been generated against lymphocyte specific antigens. Evidence is presented that not only the LTA but also the PAA is a direct effect of both HATG and SA beta 2mG on lymphocytes and platelets. The specificity of the antibodies was investigated by means of purified human urinary beta-2-microglobulin (beta 2m). Beta-2-microglobulin had no detectable inhibitory effect on the LTA and, in most cases, on the PAA of HATG. Even in a highly sensitive assay system, no more than 5 to 7% of the total PAA of HATG was inhibitable by beta 2m. In contrast, both the PAA and LTA of SA beta 2mG could be inhibited by beta 2m in a time- and dose-dependent fashion. The results prove that HATG and SA beta 2mG exert their actions through different membrane components on both platelets and lymphocytes. This is consistent with our earlier observation that the PAA of HATG and SA beta 2mG may widely dissociate among various human platelet-rich plasmas. Relatively low response to anti-beta 2m in the presence of high reactivity to ALG/ATG can also be explained by varying plasma levels of beta 2m. Finally, inhibition of the PAA of SA beta 2mG by purified beta 2m provides the first model where the platelet aggregating effect on an inducer (anti-beta 2m) can quantitatively be blocked by its specific "solubilized" receptor (beta 2m) whose structure is fully understood.