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The Effects of Affinity Mediated Clonal Expansion of Premigrant Thymocytes on the Periphery T-Cell Repertoire
The immune system maintains a highly diverse T-cell repertoire,
which is shaped by active interactions between developing thymocytes
and endogenous peptide/MHC molecules through the principle of
positive and negative selections. Detours et al. developed a
quantitative model addressing key immunologic notions such as
selection, alloreactivity, and self-restriction. The model was based
on the assumption that the clone size is uniformly distributed in
the naive T-cell repertoire. However, recent biological findings
have indicated that the naive T-cell repertoire is highly skewed,
due to the uneven proliferation of premigrant single-positive
thymocytes. In this paper, the model is revised to include these new
findings. The effects of the uneven clonal expansion are investigated in detail
and their biological significance is discussed. It is found that the
uneven clonal expansion can significantly enhance the self-MHC
restriction, while avoiding decreasing the alloreactivity. The clonal expansion
therefore appears to be an additional selection event, resulting in
fine tuning of the repertoire. In this way, T-cells reaching the
periphery pool can fulfill maximum competence: both high
self-restriction and high alloreactivity.