TY - JOUR
T1 - Lower receptor avidity required for thymic clonal deletion than for effector T-cell function
AU - Pircher, Hanspeter
AU - Rohrer, Urs Hoffmann
AU - Moskophidis, Demetrius
AU - Zinkernagel, Rolf M.
AU - Hengartner, Hans
PY - 1991
Y1 - 1991
N2 - CLONAL deletion in the thymus plays a major part in T-cell tolerance to self antigens1-3. But the mechanism of negative selection, its fine specificity and the threshold of affinity and avidity remains unknown. We have now examined these aspects of negative selection with mice expressing a transgenic T-cell receptor with specificity for lymphocytic choriomeningitis virus (LCMV) glycoprotein in association with the class I H-2Db molecule. These mice were rendered tolerant to LCMV by neonatal infection with mutant LCMVs hearing point mutations in the T-cell epitope recognized by the transgenic T-cell receptor (ref. 4). Variant LCMVs were also tested for their ability to elicit antiviral responses in transgenic mice in vivo and in vitro. Comparison in vivo revealed that a low-avidity receptor interaction, which was unable to induce effector T cells in the periphery, was still sufficient for clonal deletion in the thymus.
AB - CLONAL deletion in the thymus plays a major part in T-cell tolerance to self antigens1-3. But the mechanism of negative selection, its fine specificity and the threshold of affinity and avidity remains unknown. We have now examined these aspects of negative selection with mice expressing a transgenic T-cell receptor with specificity for lymphocytic choriomeningitis virus (LCMV) glycoprotein in association with the class I H-2Db molecule. These mice were rendered tolerant to LCMV by neonatal infection with mutant LCMVs hearing point mutations in the T-cell epitope recognized by the transgenic T-cell receptor (ref. 4). Variant LCMVs were also tested for their ability to elicit antiviral responses in transgenic mice in vivo and in vitro. Comparison in vivo revealed that a low-avidity receptor interaction, which was unable to induce effector T cells in the periphery, was still sufficient for clonal deletion in the thymus.
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U2 - 10.1038/351482a0
DO - 10.1038/351482a0
M3 - Article
C2 - 1710780
AN - SCOPUS:0025761241
SN - 0028-0836
VL - 351
SP - 482
EP - 485
JO - Nature
JF - Nature
IS - 6326
ER -