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CIITA-regulated plexin-A1 affects T-cell–dendritic cell interactions

Nature Immunology volume 4, pages 891–898 (2003)Cite this article

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Abstract

The major histocompatibility complex (MHC) class II transactivator (CIITA) is the 'master coactivator' of MHC class II genes. To identify new targets of CIITA, we analyzed cDNA microarrays of dendritic cells (DCs) from CIITA-deficient, MHC class II–deficient and control mice. We found the semaphorin receptor plexin-A1 was expressed in DCs, but not in other immune cells, and was strongly induced by CIITA. RNA interference by short hairpin RNA specific for plexin-A1, but not a single-nucleotide mutant, greatly reduced plexin-A1 expression and T cell stimulation by protein- or peptide-antigen–pulsed DCs.Plexin-A1 is not required for peptide binding to MHC. These data indicate involvement of plexin-A1 in T cell–DC interactions but not antigen processing or binding.

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Figure 1: Plexin-A1 expression is decreased in DCs from CIITA-deficient mice relative to its expression in DCs from MHC class II–deficient and wild-type mice.
Figure 2: CIITA activates the Plxna1 promoter.
Figure 3: Reduction of plexin-A1 expression in 3B11 DC cells by stable transfection with a plexin-A1 shRNA expression vector.
Figure 4: Plexin-A1 does not affect expression of cell surface molecules but is important for allostimulatory activity in vitro and in vivo.
Figure 5: Processing and presentation of OVA by plexin shRNA 3B11 cells.

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  • 22 August 2003

    appended AOP PDF with erratum (will be corrected for print issue) and placed footnote in SGML

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Acknowledgements

We thank S. Strittmatter for donation of the plexin-A1 antibody. This work was supported by grants AI29564, AI54309, NS34910 and DK38108 from the National Institutes of Health and grant RG1785 from the National Multiple Sclerosis Society to J.P.-Y.T. and National Institutes of Health grant A149589 to J.S.B.

*Note: In the version of this article originally published online, the ninth subheading in the Methods section was printed incorrectly. The correct subheading should read "Activation of T-cell hybridoma with 3B11 cells pulsed with OVA whole protein or peptide." This error has been corrected for the online and print versions of the article.

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Authors and Affiliations

  1. Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Athena W Wong & Jenny P-Y Ting

  2. Department of Microbiology and Immunology and the Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Athena W Wong, W June Brickey, Debra J Taxman, Karen P McKinnon & Jenny P-Y Ting

  3. Department of Medicine, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Hendrick W van Deventer

  4. Department of Pediatrics and Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    William Reed

  5. Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, 43210, Ohio, USA

    Jian Xin Gao, Pan Zheng & Yang Liu

  6. Department of Microbiology and Immunology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, 46202, Indiana, USA

    Ping Li & Janice S Blum

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Correspondence to Jenny P-Y Ting.

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Wong, A., Brickey, W., Taxman, D. et al. CIITA-regulated plexin-A1 affects T-cell–dendritic cell interactions. Nat Immunol 4, 891–898 (2003). https://doi.org/10.1038/ni960

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