TY - JOUR
T1 - T cells in mice expressing a transgenic human TCRβ chain get positively selected but cannot be activated in the periphery by signaling through TCR
AU - Pasare, Chandrashekhar
AU - Mukherjee, Paushali
AU - Verhoef, Adrienne
AU - Bansal, Pratima
AU - Mendiratta, Sanjeev K.
AU - George, Anna
AU - Lamb, Jonathan R.
AU - Rath, Satyajit
AU - Bal, Vineeta
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Repertoire development
KW - Signal transduction
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U2 - 10.1093/intimm/13.1.53
DO - 10.1093/intimm/13.1.53
M3 - Article
C2 - 11133834
AN - SCOPUS:0035187740
SN - 0953-8178
VL - 13
SP - 53
EP - 62
JO - International Immunology
JF - International Immunology
IS - 1
ER -