Broad cross-reactivity of the T-cell repertoire achieves specific and sufficiently rapid target searching
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arXiv
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| Format: | Preprint |
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2017
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| _version_ | 1866913233716117504 |
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| author | Xu, Jin Jo, Junghyo |
| author_facet | Xu, Jin Jo, Junghyo |
| contents | 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. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_1712_04633 |
| institution | arXiv |
| publishDate | 2017 |
| record_format | arxiv |
| spellingShingle | Broad cross-reactivity of the T-cell repertoire achieves specific and sufficiently rapid target searching Xu, Jin Jo, Junghyo Cell Behavior 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. |
| title | Broad cross-reactivity of the T-cell repertoire achieves specific and sufficiently rapid target searching |
| topic | Cell Behavior |
| url | https://arxiv.org/abs/1712.04633 |