MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Ursula B. Fischer, Erica L. Jacovetty, Ricardo B. Medeiros, Brian D. Goudy, Traci Zell, Jeannie Beth Swanson, Elizabeth Lorenz, Yoji Shimizu, Mark J. Miller, Alexander Khoruts, Elizabeth Ingulli

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The role continuous contact with self-peptide/MHC molecules (self ligands) in the periphery plays in the function of mature T cells remains unclear. Here, we elucidate a role for MHC class II molecules in T cell trafficking and antigen responsiveness in vivo. We find that naïve CD4 T cells deprived of MHC class II molecules demonstrate a progressive and profound defect in motility (measured by real-time two-photon imaging) and that these cells have a decreased ability to interact with limiting numbers of cognate antigen-bearing dendritic cells, but they do not demonstrate a defect in their responsiveness to direct stimulation with anti-CD3 monoclonal antibody. Using GST fusion proteins, we show that MHC class II availability promotes basal activation of Rap1 and Rac1 but does not alter the basal activity of Ras. We propose that tonic T cell receptor signaling from self-ligand stimulation is required to maintain a basal state of activation of small guanosine triphosphatases critical for normal T cell motility and that T cell motility is critical for the antigen receptivity of naïve CD4 T cells. These studies suggest a role for continuous self-ligand stimulation in the periphery for the maintenance and function of mature naïve CD4 T cells.

Original languageEnglish (US)
Pages (from-to)7181-7186
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number17
DOIs
StatePublished - Apr 24 2007

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Dendritic Cells
Cell Movement
T-Lymphocytes
Antigens
Ligands
Guanosine
Viral Tumor Antigens
T-Cell Antigen Receptor
Photons
Monoclonal Antibodies
Maintenance
Peptides
Proteins

Keywords

  • GTPases
  • MHC class II deficiency
  • Self ligand

Cite this

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo. / Fischer, Ursula B.; Jacovetty, Erica L.; Medeiros, Ricardo B.; Goudy, Brian D.; Zell, Traci; Swanson, Jeannie Beth; Lorenz, Elizabeth; Shimizu, Yoji; Miller, Mark J.; Khoruts, Alexander; Ingulli, Elizabeth.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 17, 24.04.2007, p. 7181-7186.

Research output: Contribution to journalArticle

Fischer, Ursula B. ; Jacovetty, Erica L. ; Medeiros, Ricardo B. ; Goudy, Brian D. ; Zell, Traci ; Swanson, Jeannie Beth ; Lorenz, Elizabeth ; Shimizu, Yoji ; Miller, Mark J. ; Khoruts, Alexander ; Ingulli, Elizabeth. / MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 17. pp. 7181-7186.
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