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- and ß-Chains Is Highly Dependent on the Level of Selecting Ligand1
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110
We have produced a TCR transgenic mouse that uses a TCR
derived from a Th1 clone that is specific for residues 64 to 76 of the
d allele of murine hemoglobin presented by I-Ek.
Examination of these TCR transgenic mice on an H-2k/k
background that expressed the nonstimulatory s allele of murine
hemoglobin revealed that these mice express many endogenous TCR chains
from both 
and ß loci. We found that this transgenic TCR is also
very inefficient at mediating ß selection, thereby showing a direct
linkage between ß selection and allelic exclusion of TCR ß. We have
also examined these mice on MHC backgrounds that have reduced levels of
I-Ek and found that positive selection of cells with high
levels of the transgenic TCR depends greatly on the ligand density.
Decreasing the selecting ligand density is a means of reducing the
number of available selecting niches, and the data reveal that the 3.L2
TCR is used sparingly for positive selection under conditions where the
number of niches becomes limiting. The results, therefore, show a way
that T cells may get to the periphery with two self-restricted TCRs:
one that efficiently mediates positive selection, and another that is
inefficient at positive selection with the available niches.
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