Coexpression of TLR2 or TLR4 with HLA-DR Potentiates the Superantigenic Activities of Mycoplasma arthritidis-Derived Mitogen

Marina T. Shio, Ghada S. Hassan, Waris A. Shah, Amal Nadiri, Youssef El Fakhry, Hogmin Li, Walid Mourad

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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. The Journal of Immunology, 2014, 192: 2543-2550.

Original languageEnglish (US)
Pages (from-to)2543-2550
Number of pages8
JournalJournal of Immunology
Volume192
Issue number6
DOIs
StatePublished - Mar 15 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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