ABSTRACT
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.
