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We present a probabilistic T-cell model that includes negative selection andtakes contrasting models of tissue-restricted antigen (TRA) expression in thethymus into account. We start from the basic model of van den Berg, Rand, andBurroughs (2001) and include negative selection via individual-based T-cellmodelling, in which each T-cell is defined by its stimulation rates to allrelevant self antigens. We present a simulation approach based on partialtilting of the stimulation rates recognized by a single T-cell. We investigatethe effects of negative selection for diverging modes of thymic antigenpresentation, namely arbitrary TRA presentation, and more or less strictemulation of tissue-specific cell lines. We observe that negative selectionleads to truncation of the tail of the distribution of the stimulation ratesmature T-cells receive from self antigens, i.e., the self background isreduced. This increases the activation probabilities of single T-cells in thepresence of non-self antigens.

Rare event simulation in immune biology: Models of negative selection in T-cell maturation