Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Pasare, C.
Right arrow Articles by Bal, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pasare, C.
Right arrow Articles by Bal, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol. 13, No. 1, 53-62, January 2001
© 2001 Japanese Society for Immunology

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

Chandrashekhar Pasare, Paushali Mukherjee, Adrienne Verhoef1, Pratima Bansal, Sanjeev K. Mendiratta, Anna George, Jonathan R. Lamb2, Satyajit Rath and Vineeta Bal

National Institute of Immunology, Aruna Asaf Ali Road, New Delhi 110 067, India
1 Department of Biology, Imperial College of Science, Technology and Medicine, London SW7 2AZ, UK
2 Respiratory Medicine Unit, University of Edinburgh, Edinburgh EH8 9AG, UK

Correspondence to: V. Bal

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 TCRß 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-CD3{epsilon} mAb triggered equivalent proliferation from Tg and non-Tg T cells, but an anti-human TCRß 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 TCRß could induce some activation markers on T cells and cross-linking of the Tg TCR by plate-coated anti-human TCRß efficiently induced T cell proliferation. Human TCRß-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 TCRß 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.

Keywords: signal transduction, repertoire development

Transmitting editor: A. J. McMichael


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.