β2-Microglobulin Identified as an Apoptosis-Inducing Factor and Its Characterization
1999; Elsevier BV; Volume: 94; Issue: 8 Linguagem: Inglês
10.1182/blood.v94.8.2744.420k34_2744_2753
ISSN1528-0020
AutoresMasaki Mori, Yasuhito Terui, Masayuki Ikeda, Hiroshi Tomizuka, Masaya Uwai, Tadashi Kasahara, Nobuyuki Kubota, Takehito Itoh, Yuji Mishima, Miyuki Douzono-Tanaka, Muneo Yamada, Seiichi Shimamura, Jiro Kikuchi, Yusuke Furukawa, Yukihito Ishizaka, Kazuma Ikeda, Hiroyuki Mano, Keiya Ozawa, Kiyohiko Hatake,
Tópico(s)T-cell and B-cell Immunology
ResumoMajor 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.
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