Marcel Salathé

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Science

High Epitope Expression Levels Increase Competition Between T Cells

Almut Scherer, Marcel Salathé and Sebastian Bonhoeffer PLoS Computational Biology, 2(8): e109 (2006) PDF

Abstract Both theoretical predictions and experimental findings suggest that T-cell populations can compete with each other. There is some debate on whether T-cells compete for aspecific stimuli, such as access to the surface on antigen presenting cells (APCs) or for specific stimuli, such as their cognate epitope ligand. We have developed an individual-based computer simulation model to study T-cell competition. Our model shows that the expression level of foreign epitopes per APC determines whether T-cell competition is mainly for specific or aspecific stimuli. Under low epitope expression, competition is mainly for the specific epitope stimuli, and hence, different epitope-specific T-cell populations coexist readily. However, if epitope expression levels are high, aspecific competition becomes more important. Such between-specificity competition can lead to competitive exclusion between different epitope-specific T-cell populations. Our model allows us to delineate the circumstances that facilitate coexistence of T-cells of different epitope specificity. Understanding mechanisms of T-cell coexistence has important practical implications for immune therapies that require a broad immune response.