  The molecular recognition of T-cell receptors is the hallmark of the adaptive
immunity. Given the finiteness of the T-cell repertoire, individual T-cell
receptors are necessary to be cross-reactive to multiple antigenic peptides. In
this study, we quantify the variability of the cross-reactivity by using a
string model that estimates the binding affinity between two sequences of amino
acids. We examine sequences of 10,000 human T-cell receptors and 10,000
antigenic peptides, and obtain a full spectrum of cross-reactivity of the
receptor-peptide binding. Then, we find that the cross-reactivity spectrum is
broad. Some T cells are reactive to 1,000 peptides, but some T cells are
reactive to only one or two peptides. Since the degree of cross-reactivity has
a correlation with the (un)binding affinity of receptors, we further
investigate how the broad crossreactivity affects the target searching of T
cells. High cross-reactive T cells may not require many trials for searching
correct targets, but they may spend long time to unbind from incorrect targets.
In contrast, low cross-reactive T cells may not spend long time to ignore
incorrect targets, but they require many trials for screening correct targets.
We evaluate this hypothesis, and show that the broad cross-reactivity of the
natural T-cell repertoire can balance the trade-off between the rapid screening
and unbinding penalty.
