Small-molecular compounds enhance the loading of APC with encephalitogenic MBP protein.
Small-molecular compounds with hydrogen bond (H-bond) donor function are able to trigger exchange reactions of MHC class II ligands. Here, we show that their effect is not limited to short peptides. Also encephalitogenic myelin basic protein (MBP) is transferred with great efficiency onto HLA-DR molecules when H-bond donor molecules such as parachlorphenol (pCP) are present. The effect was observed not only with soluble MHC class II but also with HLA-DR1 and HLA-DR2 molecules on the cell surface. The improved loading of APC translates directly into improved T cell activation. In the presence of pCP T cells reacted at significantly lower antigen concentrations, an effect observed with purified MBP protein as well as with crude spinal cord homogenate. The 'accidental' transfer of autoantigens such as MBP onto activated APC might trigger fatal autoimmune reactions and small molecules as catalysts of this process could represent risk factors, which had not been accounted for as yet.
Marin-Esteban
Viviana
V
Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
Falk
Kirsten
K
Rötzschke
Olaf
O
D000938:Antigen-Presenting Cells / Q000378:metabolism*; D004660:Encephalitis / Q000209:etiology*; D015802:HLA-DR2 Antigen / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D004676:Myelin Basic Protein / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D015802:HLA-DR2 Antigen; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein