First Author | Pasare C | Year | 2001 |
Journal | Int Immunol | Volume | 13 |
Issue | 1 | Pages | 53-62 |
PubMed ID | 11133834 | Mgi Jnum | J:128806 |
Mgi Id | MGI:3768038 | Doi | 10.1093/intimm/13.1.53 |
Citation | Pasare C, et al. (2001) T cells in mice expressing a transgenic human TCR beta chain get positively selected but cannot be activated in the periphery by signaling through TCR. Int Immunol 13(1):53-62 |
abstractText | 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 TCRbeta 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-CD3epsilon mAb triggered equivalent proliferation from Tg and non-Tg T cells, but an anti-human TCRbeta 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 CD44(high), whereas most transgene-expressing T cells remained CD44(low), suggesting that transgene-expressing cells are not activated in the periphery to participate in immune responses. However, anti-human TCRbeta could induce some activation markers on T cells and cross-linking of the Tg TCR by plate-coated anti-human TCRbeta efficiently induced T cell proliferation. Human TCRbeta-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 TCRbeta 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. |