Rv2468c, a novel Mycobacterium tuberculosis protein that costimulates human CD4 + T cells through VLA-5

Qing Li, Xuedong Ding, Jeremy J. Thomas, Clifford V. Harding, Nicole D. Pecora, Assem G. Ziady, Samuel Shank, W. Henry Boom, Christina L. Lancioni, Roxana E. Rojas

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Mtb regulates many aspects of the host immune response, including CD4 + T lymphocyte responses that are essential for protective immunity to Mtb, and Mtb effects on the immune system are paradoxical, having the capacity to inhibit (immune evasion) and to activate (adjuvant effect) immune cells. Mtb regulates CD4 + T cells indirectly (e.g., by manipulation of APC function) and directly, via integrins and TLRs expressed on T cells. We now report that previously uncharacterized Mtb protein Rv2468c/MT2543 can directly regulate human CD4 + T cell activation by delivering costimulatory signals. When combined with TCR stimulation (e.g., anti-CD3), Rv2468c functioned as a direct costimulator for CD4 + T cells, inducing IFN-7 secretion and T cell proliferation. Studies with blocking antibodies and soluble RGD motifs demonstrated that Rv2468c engaged integrin VLA-5 (a5/31) on CD4 + T cells through its FN-like RGD motif. Costimulation by Rv2468c induced phosphorylation of FAKs and Pyk2. These results reveal that by expressing molecules that mimic host protein motifs, Mtb can directly engage receptors on CD4 + T cells and regulate their function. Rv2468c-induced costimulation of CD4 + T cells could have implications for TB immune pathogenesis and Mtb adjuvant effect.

Original languageEnglish (US)
Pages (from-to)311-320
Number of pages10
JournalJournal of Leukocyte Biology
Volume91
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • FAK
  • Fibronectin
  • Pyk2
  • RGD motif
  • α5β1 integrin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Li, Q., Ding, X., Thomas, J. J., Harding, C. V., Pecora, N. D., Ziady, A. G., Shank, S., Boom, W. H., Lancioni, C. L., & Rojas, R. E. (2012). Rv2468c, a novel Mycobacterium tuberculosis protein that costimulates human CD4 + T cells through VLA-5. Journal of Leukocyte Biology, 91(2), 311-320. https://doi.org/10.1189/jlb.0711364