T cells in mice expressing a transgenic human TCRβ chain get positively selected but cannot be activated in the periphery by signaling through TCR

Chandrashekhar Pasare, Paushali Mukherjee, Adrienne Verhoef, Pratima Bansal, Sanjeev K. Mendiratta, Anna George, Jonathan R. Lamb, Satyajit Rath, Vineeta Bal

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

TCR-CD3 complex-mediated signaling is crucial for both developmental selection and antigenic activation of T cells. We report that mice expressing a recombined human TCRβ chain (Tg), which have normal development of T cells, mounted very weak responses to immunization with protein antigens as well as the HA307-319 peptide recognized by the human T cell clone HA1.7 from which the transgene is derived. An anti-CD3ε mAb triggered equivalent proliferation from Tg and non-Tg T cells, but an anti-human TCRβ mAb induced proliferation poorly in Tg T cells in contrast to human T cells or HA1.7. In Tg mice, T cells expressing endogenous TCR were CD44high, whereas most transgene-expressing T cells remained CD44low, suggesting that transgene-expressing cells are not activated in the periphery to participate in immune responses. However, anti-human TCRβ could induce some activation markers on T cells and cross-linking of the Tg TCR by plate-coated anti-human TCRβ efficiently induced T cell proliferation. Human TCRβ-mediated Tg T cell activation could be rescued by exogenous IL-2, as well as by the calcium ionophore A23187, but not by phorbol esters. Thus, this human TCRβ chain functions efficiently for positive selection of mouse T cells, but not for their peripheral activation, probably because of a lack of oligomerization leading to defects in signaling for calcium flux and IL-2 induction. The data thus suggest an early point of separation of signaling pathways between positive selection and peripheral activation of T cells.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalInternational Immunology
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Repertoire development
  • Signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pasare, C., Mukherjee, P., Verhoef, A., Bansal, P., Mendiratta, S. K., George, A., Lamb, J. R., Rath, S., & Bal, V. (2001). T cells in mice expressing a transgenic human TCRβ chain get positively selected but cannot be activated in the periphery by signaling through TCR. International Immunology, 13(1), 53-62. https://doi.org/10.1093/intimm/13.1.53