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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.

No MeSH data available.


Discrimination score as a function of ΔTconv and ΔTreg.The color represents the maximum value of the discrimination score S. The maximization of S is taken over the basal reproduction activity α. μTconv,self and μTreg,non−self are set to −3.
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pone.0163134.g004: Discrimination score as a function of ΔTconv and ΔTreg.The color represents the maximum value of the discrimination score S. The maximization of S is taken over the basal reproduction activity α. μTconv,self and μTreg,non−self are set to −3.

Mentions: Fig 4 shows the maximum value of the discrimination score S as a function of ΔTconv and ΔTreg obtained with Treg regulation. The maximization of S is taken over the basal reproduction activity α. As shown, the maximum discrimination score takes larger values in a relatively narrow range of ΔTreg (e.g., 0.25 < ΔTreg < 0.75). The maximum discrimination score becomes small when ΔTreg is large, because in this region the active proliferation of Tconv cells is suppressed by Treg cells for both self and non-self antigen presentation. In contrast, the maximum discrimination score monotonically increases with increasing ΔTconv. The dependency of discrimination performance on the affinity biases ΔTconv and ΔTreg is robust on changing model rules and parameters, suggesting it is a general feature of this Treg-driven self/non-self discrimination.


Robust and Accurate Discrimination of Self/Non-Self Antigen Presentations by Regulatory T Cell Suppression
Discrimination score as a function of ΔTconv and ΔTreg.The color represents the maximum value of the discrimination score S. The maximization of S is taken over the basal reproduction activity α. μTconv,self and μTreg,non−self are set to −3.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5036821&req=5

pone.0163134.g004: Discrimination score as a function of ΔTconv and ΔTreg.The color represents the maximum value of the discrimination score S. The maximization of S is taken over the basal reproduction activity α. μTconv,self and μTreg,non−self are set to −3.
Mentions: Fig 4 shows the maximum value of the discrimination score S as a function of ΔTconv and ΔTreg obtained with Treg regulation. The maximization of S is taken over the basal reproduction activity α. As shown, the maximum discrimination score takes larger values in a relatively narrow range of ΔTreg (e.g., 0.25 < ΔTreg < 0.75). The maximum discrimination score becomes small when ΔTreg is large, because in this region the active proliferation of Tconv cells is suppressed by Treg cells for both self and non-self antigen presentation. In contrast, the maximum discrimination score monotonically increases with increasing ΔTconv. The dependency of discrimination performance on the affinity biases ΔTconv and ΔTreg is robust on changing model rules and parameters, suggesting it is a general feature of this Treg-driven self/non-self discrimination.

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.