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.