Macrophage migration inhibitory factor has a MHC class I-like motif and function.
Macrophage migration inhibitory factor (MIF) is found in immune-privileged sites and inhibits cytotoxicity mediated by CD3-ve lymphokine-activated killer cells (LAK). The mechanism by which MIF attenuates LAK cytotoxicity is unknown. We provide evidence that MIF has a major histocompatibility complex (MHC) class I-like motif. A monoclonal antibody (OX18) that binds a conserved region of rat MHC class I proteins binds native MIF. Anti-MIF polyclonal antibodies bind MHC class I. Epitope mapping suggests OX18 binds a loop of MHC class I bound by several receptors for MHC class I. A sequence (PRPEG) within the proposed OX18-binding site on MHC class I exists with a short insertion in MIF. OX18 does not bind MIF that is denatured by SDS-PAGE. This suggests the OX18 epitope is dependent on higher order structure in MIF. Interestingly, MIF inhibits binding of tetramers of MHC class I (H2D(b)) to LAK cells, suggesting it may bind to receptors for MHC class I. MIF may be an example where small regions of MHC class I are used by endogenous and viral proteins to control cytotoxicity mediated by immune cells.
Gibbings
D J
DJ
Department of Medicine, Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada. gibbings@ualberta.ca
Ghetu
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Dery
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Befus
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D020816:Amino Acid Motifs; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D018604:Epitope Mapping; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000276:immunology* / Q000302:isolation & purification; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology* / Q000302:isolation & purification; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051381:Rats
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse