Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Immune regulation

BTLA finds its true partner

Nature Reviews Immunology volume 5, page 8 (2005)Cite this article

The observation that binding of a B7X–Fc fusion protein to BTLA-deficient lymphocytes was reduced compared with binding to BTLA-sufficient lymphocytes led to the idea that B7X might be a BTLA ligand. So, Sedy et al. set out to find further evidence of this interaction. However, BTLA tetramers did not bind a B7X-expressing fibroblast cell line, and a B7X–Fc fusion protein did not bind BTLA-expressing cell lines. So, further studies in search of a BTLA-binding partner were carried out.

The physiological ligand for BTLA was first characterized using a BTLA–Fc fusion protein and was found to be expressed by resting T cells. A subsequent cDNA-library screen for cDNA encoding a BTLA-tetramer-binding protein indicated that the tumour-necrosis-factor receptor (TNFR)-family member HVEM was the BTLA-binding protein. Further studies then showed that BTLA bound the most membrane-distal cysteine-rich domain of HVEM. Binding of HVEM to BTLA induced tyrosine phosphorylation of BTLA and its association with SHP2 (SRC-homology-2-domain-containing protein tyrosine phosphatase 2). Furthermore, HVEM expression by antigen-presenting cells impaired peptide-mediated T-cell stimulation (in the presence or absence of co-stimulation) in a manner that was dependent on T-cell expression of BTLA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

ORIGINAL RESEARCH PAPER

  1. Sedy, J. R. et al. B and T lymphocyte attenuator regulates T cell activation with herpesvirus entry mediator. Nature Immunol. 6, 90–98 (2005).

    Article  CAS  Google Scholar 

Download references

Authors
  1. Karen Honey
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Honey, K. BTLA finds its true partner. Nat Rev Immunol 5, 8 (2005). https://doi.org/10.1038/nri1541

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nri1541

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing