Mechanism of human interferon-γ production: Involvement of β-2-microglobulin

Abstract

The ability of several monoclonal antibodies (MoAbs) against β-2-microglobulin (β2m) to inhibit interferon-γ (IFN) production was assayed in peripheral blood mononuclear cells (PBMC). All of them strongly reduce IFN-γ 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-β2m MoAbs do not effectively reduce IFN-γ 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-β2m antibodies was specific for β2m protein, and (ii) β2m is not itself the site of action of GO. Moreover, it is demonstrated that the addition of β2m to oxidated PBMC strongly enhances subsequent IFN-γ production. Oxidation of galactose residues on glycoproteins of macrophage membrane is an obligate step for IFN-γ induction whatever the inducer, thus our results suggest that β2m is involved in the mechanism of induction of IFN-γ.