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Macrophage Migration Inhibitory Factor Has a MHC class I‐Like Motif and Function
Author(s) -
Gibbings D. J.,
Ghetu A. F.,
Dery R.,
Befus A. D.
Publication year - 2008
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2007.02046.x
Subject(s) - cd74 , macrophage migration inhibitory factor , mhc class i , major histocompatibility complex , mhc restriction , biology , mhc class ii , lymphokine , polyclonal antibodies , cd8 , epitope , microbiology and biotechnology , immune system , antibody , immunology , cytokine
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.