Mechanism of human interferon-gamma production: involvement of beta-2-microglobulin.
The ability of several monoclonal antibodies (MoAbs) against beta-2-microglobulin (beta 2m) to inhibit interferon-gamma (IFN) production was assayed in peripheral blood mononuclear cells (PBMC). All of them strongly reduce IFN-gamma induction by galactose oxidase (GO), a well-characterized enzyme capable of activating T lymphocytes through mediation of macrophages. In contrast, many MoAbs directed against HLA class I (heavy chain) and class II antigens do not inhibit IFN induction by GO. On the other hand, anti-beta 2m MoAbs do not effectively reduce IFN-gamma induction by A23187, a calcium ionophore that acts on T cells in the absence of accessory cells. Competition experiments demonstrate that (i) the inhibition of anti-beta 2m antibodies was specific for beta 2m protein, and (ii) beta 2m is not itself the site of action of GO. Moreover, it is demonstrated that the addition of beta 2m to oxidated PBMC strongly enhances subsequent IFN-gamma production. Oxidation of galactose residues on glycoproteins of macrophage membrane is an obligate step for IFN-gamma induction whatever the inducer, thus our results suggest that beta 2m is involved in the mechanism of induction of IFN-gamma.
D000911:Antibodies, Monoclonal / Q000502:physiology; D000918:Antibody Specificity; D000001:Calcimycin / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005692:Galactose Oxidase / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology; D007369:Interferon Inducers / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007369:Interferon Inducers; D001613:beta 2-Microglobulin; D000001:Calcimycin; D007371:Interferon-gamma; D005692:Galactose Oxidase