beta(2)-microglobulin identified as an apoptosis-inducing factor and its characterization

Major histocompatibility complex (MHC) molecules play an important role in antigen presentation for induction of tumor as well as cellular and humoral immunities. Recent studies using anti-MHC antibodies demonstrated that ant ibodies specific for HLA class I molecules induced cellular activation and a type of apoptosis that may be distinct from Fas-dependent or TNFR (tumor necrosis factor-alpha receptor)-dependent processes. We purified a previous ly untested apoptosis-inducing factor from HL-60 human leukemic cell-condit ioned media to homogeneity and sequenced it. It was identified as beta(2)-m icroglobulin (beta(2)m), which has been previously known as thymotaxin and is a part of the HLA class I antigen complex. beta(2)m acts on both T-leuke mic cells and myeloid leukemic cells to induce apoptosis, which then activa tes caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2) m recognized an epitope distinct from those recognized by the anti-HLA clas s I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination o f tumor cells, which occurs as a result of the action of beta(2)m as an apo ptosis-inducing factor. (C) 1999 by The American Society of Hematology.