Coexpression of TLR2 or TLR4 with HLA-DR potentiates the superantigenic activities of Mycoplasma arthritidis-derived mitogen.
Mycoplasma arthritidis-derived mitogen (MAM) is a member of the superantigen family that structurally differs from other members while still capable of initiating cognate APC/T cell interaction. In addition to the critical role of MHC class II molecules, it has been suggested that TLR2 and TLR4 may cooperate with MHC class II during MAM-induced responses. In this study, we investigated the direct involvement of TLR2 and TLR4 in MAM binding and presentation to T cells. Our results showed that MAM fails to bind to TLR2- and TLR4-transfected cells. However, coexpression of TLR2 or TLR4 with HLA-DR significantly increases MAM binding and the subsequent T cell activation compared with cells expressing HLA-DR alone. The upregulated MAM binding and activity in HLA-DR/TLR-transfected cells is abrogated by an anti-HLA-DR Ab. Interestingly, we also found that MAM complexed with soluble HLA-DR is capable of binding to both TLR2 and TLR4. The enhancing effect of TLR2 or TLR4 on MAM-induced T cell proliferation was not due to TLR ligand contamination in the MAM preparation. Taken together, these results strongly suggest that binding of MAM to HLA-DR leads to a conformational change in MAM structure allowing its interaction with TLR2 and TLR4 and a better recognition by T cells.
Laboratoire d'immunologie cellulaire et moléculaire, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec H2X 0A9, Canada;
Marina T
MT
Shio
Ghada S
GS
Hassan
Waris A
WA
Shah
Amal
A
Nadiri
Youssef
Y
El Fakhry
Hogmin
H
Li
Walid
W
Mourad
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D057809:HEK293 Cells; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D011485:Protein Binding / Q000276:immunology; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D007376:Interleukin-2; C052996:Mycoplasma arthritidis mitogen; D018089:Superantigens; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4