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Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression

View Article: PubMed Central - PubMed

ABSTRACT

The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification.

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The dynamic change of T cell number in response to antigen presentation.(a) Response to a non-self antigen presentation. At time = 0 (denoted by arrow), an non-self antigen is presented in APCs with the ratio rt = 0.3. In the figures, time series data obtained by 10 different initial conditions are overlaid. (b) Response to stopping a non-self antigen presentation. At time = 0, the presented non-self antigen on APCs is replaced by randomly chosen self antigens. The parameters are set to those used in Fig 2.
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pone.0163134.g005: The dynamic change of T cell number in response to antigen presentation.(a) Response to a non-self antigen presentation. At time = 0 (denoted by arrow), an non-self antigen is presented in APCs with the ratio rt = 0.3. In the figures, time series data obtained by 10 different initial conditions are overlaid. (b) Response to stopping a non-self antigen presentation. At time = 0, the presented non-self antigen on APCs is replaced by randomly chosen self antigens. The parameters are set to those used in Fig 2.

Mentions: Fig 5 presents the dynamic change of T cell number over time in response to antigen presentation. Fig 5(a) shows the response to a non-self antigen presentation at time = 0 (denoted by arrow), in which time series data obtained by different initial conditions are overlaid. As shown, the response time to reach the new steady state fluctuates over samples. In contrast, when the non-self antigen presentation stops and all APCs start to present randomly chosen self antigens, the number of T cells quickly falls into the original steady state as shown in Fig 5(b). These results indicated that, in the former case, some time is necessary to find and to amplify Tconv cells which have high affinity to the presented non-self antigen.


Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression
The dynamic change of T cell number in response to antigen presentation.(a) Response to a non-self antigen presentation. At time = 0 (denoted by arrow), an non-self antigen is presented in APCs with the ratio rt = 0.3. In the figures, time series data obtained by 10 different initial conditions are overlaid. (b) Response to stopping a non-self antigen presentation. At time = 0, the presented non-self antigen on APCs is replaced by randomly chosen self antigens. The parameters are set to those used in Fig 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036821&req=5

pone.0163134.g005: The dynamic change of T cell number in response to antigen presentation.(a) Response to a non-self antigen presentation. At time = 0 (denoted by arrow), an non-self antigen is presented in APCs with the ratio rt = 0.3. In the figures, time series data obtained by 10 different initial conditions are overlaid. (b) Response to stopping a non-self antigen presentation. At time = 0, the presented non-self antigen on APCs is replaced by randomly chosen self antigens. The parameters are set to those used in Fig 2.
Mentions: Fig 5 presents the dynamic change of T cell number over time in response to antigen presentation. Fig 5(a) shows the response to a non-self antigen presentation at time = 0 (denoted by arrow), in which time series data obtained by different initial conditions are overlaid. As shown, the response time to reach the new steady state fluctuates over samples. In contrast, when the non-self antigen presentation stops and all APCs start to present randomly chosen self antigens, the number of T cells quickly falls into the original steady state as shown in Fig 5(b). These results indicated that, in the former case, some time is necessary to find and to amplify Tconv cells which have high affinity to the presented non-self antigen.

View Article: PubMed Central - PubMed

ABSTRACT

The immune response by T cells usually discriminates self and non-self antigens, even though the negative selection of self-reactive T cells is imperfect and a certain fraction of T cells can respond to self-antigens. In this study, we construct a simple mathematical model of T cell populations to analyze how such self/non-self discrimination is possible. The results demonstrate that the control of the immune response by regulatory T cells enables a robust and accurate discrimination of self and non-self antigens, even when there is a significant overlap between the affinity distribution of T cells to self and non-self antigens. Here, the number of regulatory T cells in the system acts as a global variable controlling the T cell population dynamics. The present study provides a basis for the development of a quantitative theory for self and non-self discrimination in the immune system and a possible strategy for its experimental verification.

No MeSH data available.


Related in: MedlinePlus