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

Blood. 1999 Oct 15;94(8):2744-53.

Abstract

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 antibodies 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 previously untested apoptosis-inducing factor from HL-60 human leukemic cell-conditioned media to homogeneity and sequenced it. It was identified as beta(2)-microglobulin (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-leukemic cells and myeloid leukemic cells to induce apoptosis, which then activates caspase 1 and 3. Cross-linking studies showed that biotinilated beta(2)m recognized an epitope distinct from those recognized by the anti-HLA class I antibody, as reported previously. We demonstrated that beta(2)m plays a previously unrecognized and important role in regulating the elimination of tumor cells, which occurs as a result of the action of beta(2)m as an apoptosis-inducing factor.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis / drug effects*
  • Culture Media, Conditioned / chemistry
  • Cysteine Proteinase Inhibitors / pharmacology
  • Fas Ligand Protein
  • HL-60 Cells / chemistry
  • Humans
  • K562 Cells / drug effects
  • Membrane Glycoproteins / physiology
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / isolation & purification
  • Neoplasm Proteins / pharmacology
  • Neoplasm Proteins / physiology
  • Oligopeptides / pharmacology
  • Receptors, Tumor Necrosis Factor / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured / drug effects
  • Tumor Necrosis Factor-alpha / physiology
  • U937 Cells / drug effects
  • beta 2-Microglobulin / immunology
  • beta 2-Microglobulin / isolation & purification
  • beta 2-Microglobulin / pharmacology*
  • beta 2-Microglobulin / physiology
  • fas Receptor / physiology

Substances

  • Amino Acid Chloromethyl Ketones
  • Antibodies, Monoclonal
  • Culture Media, Conditioned
  • Cysteine Proteinase Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Oligopeptides
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • beta 2-Microglobulin
  • fas Receptor
  • L 709049