Involvement of zinc in the binding of Mycoplasma arthritidis-derived mitogen to the proximity of the HLA-DR binding groove regardless of histidine 81 of the beta chain.
Although our recent studies have provided the first evidence demonstrating the direct binding of Mycoplasma arthritidis-derived mitogen (MAM) to MHC class II molecules, it is not yet established how MAM interacts with these molecules. Herein, we demonstrate that MAM binds preferentially and with high affinity to HLA-DR molecules in a zinc-dependent manner. MAM's affinity (25 nM) for HLA-DR molecules is comparable to that of staphylococcal superantigens, and is slightly higher than that for murine MHC class II molecules expressed on the A20 B cell line (111 nM). The amino acid residues located between 14 - 31 and 76 - 90 of the MAM N-terminus play a critical role in MAM / HLA-DR interactions. Histidine at position 81 of the HLA-DR beta-chain, known to be critical for binding of zinc-coordinated superantigens, is not necessary for MAM / HLA-DR interactions. The HLA-DR residues involved in MAM binding are located in the proximal binding groove of the HLA-DR molecule, where the nature of the peptide of the binding groove plays an important role in MAM / HLA-DR interaction. This is the first detailed characterization of MAM's interactions with MHC class II molecules showing a mode of interaction with HLA-DR distinct from that of other superantigens.
Etongué-Mayer
Pierre
P
Centre de Recherche en Rhumatologie et Immunologie, CHUQ, Pavillon CHUL and Laval University, St-Foy, Canada.
Langlois
Marc-André
MA
Ouellette
Marc
M
Li
Hongmin
H
Younes
Souheil
S
Al-Daccak
Reem
R
Mourad
Walid
W
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial; D001402:B-Lymphocytes; D001483:Base Sequence; D001665:Binding Sites; D002461:Cell Line, Transformed; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006639:Histidine / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011506:Proteins; D018089:Superantigens; D015032:Zinc / Q000378:metabolism*
D000941:Antigens; D000942:Antigens, Bacterial; D015798:HLA-DR1 Antigen; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D010455:Peptides; D011506:Proteins; D018089:Superantigens; D006639:Histidine; D015032:Zinc