Molecular Interaction and Enzymatic Activity of Macrophage Migration Inhibitory Factor with Immunorelevant Peptides

Abstract

Disulfide reduction is an important step in antigen processing for HLA class II restricted T cell responses. Migration inhibitory factor (MIF) is a member of the thioredoxin family and has been classically defined as a cytokine. Using enzyme-linked immunosorbent assay and CD analysis, here we describe the binding to MIF of two peptides, hepatitis B surface antigen (HBsAg) and insulin B (InsB) with high affinity for HLA class II allotypes, HLA-DP2 and HLA-DQ8, respectively. At neutral pH, cysteinylated InsB was a substrate for MIF thiol reductase activity, as assessed by mass spectroscopy/ electrospray analysis. Finally, a biologically active form of MIF co-immunopurified with mature forms of HLA DP2/15, and a peptide derived from the HLA-DP ␤1 helix could be used for affinity purification of MIF. The possibility that MIF participates in class II antigen presentation and/or as a chaperone is discussed.

Effect of macrophage migration inhibitory factor (MIF) gene variants and MIF serum concentrations on the risk of type 2 diabetes: results from the MONICA/KORA Augsburg Case–Cohort Study, 1984–2002

“…MIF has been described as a proinflammatory cytokine and as potentiating lipopolysaccharide-mediated immune activation [46]. MIF counter-regulates glucocorticoid-mediated immune suppression, suppresses p53 activity, has enzyme activities and may also participate in antigen presentation [1,46,47]. However, no complete signal transduction pathway is known [48].…”

Estrogen-dependent up-regulation of TRPA1 and TRPV1 receptor proteins in the rat endometrium

“…TRPA1, TRPV1 and MIF immunostaining intensity was evaluated by a semi-quantitative scoring system ranging from 0 to 3 (0, no staining; 1, weak staining in the majority of cells with only focal moderate staining; 2, moderate staining in the majority of cells with only focal strong staining; 3, strong staining in the majority of cells). The selectivity of the antibodies was proven by the lack of staining after the respective blocking peptide and literature data (Potolicchio et al 2003) respectively. The endometrial thickness was measured in five different sections of each animal and then averaged in all the experimental groups.…”

Amplification of Tumor Hypoxic Responses by Macrophage Migration Inhibitory Factor–Dependent Hypoxia-Inducible Factor Stabilization

“…Several proteins identified by yeast two-hybrid screening to interact with MIF reportedly do so through a C-X-X-C thiol reductase catalytic domain within MIF (16)(17)(18)(19). One such protein is a component of the COP9 signalosome, which makes up a part of the 26S proteasome (19).…”