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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Diversity of Antigen Receptors01:28

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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
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Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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T Cell Types and Functions01:24

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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B Cell Activation and Differentiation01:24

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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How many TCR clonotypes does a body maintain?

Grant Lythe1, Robin E Callard2, Rollo L Hoare2

  • 1Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK.

Journal of Theoretical Biology
|November 8, 2015
PubMed
Summary

T cell clonotype lifetime varies between mice and humans due to differences in peripheral division. Human clonotypes can persist for decades, expanding significantly in number.

Keywords:
Clonal repertoireCompetitionExtinctionHomeostasisStochastic modellingT cells

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Area of Science:

  • Immunology
  • Computational Biology

Background:

  • T cell clonotypes, sets of T cells sharing a T cell receptor (TCR), originate in the thymus and eventually become extinct.
  • Understanding clonotype dynamics is crucial for comprehending immune repertoire stability and function.

Purpose of the Study:

  • To calculate the mean number of cells per TCR clonotype and the total number of clonotypes in mice and humans.
  • To model the homeostasis of a multiclonal T cell population and analyze factors influencing clonotype survival and expansion.

Main Methods:

  • Utilized published estimates of total cell numbers and thymic production rates.
  • Developed and analyzed a computational model simulating T cell competition for self pMHC stimuli.
  • Modeled homeostasis through a balance of cell division, death, thymic production, and clonotype extinction.

Main Results:

  • In mice, with limited peripheral division, clonotype size is small and thymic output-dependent.
  • In humans, significant peripheral division allows clonotypes to survive for decades and expand considerably.
  • The total number of distinct human clonotypes may be only one order of magnitude less than the total naive T cell count.

Conclusions:

  • Peripheral division plays a critical role in determining T cell clonotype lifetime and size, particularly in humans.
  • Computational modeling provides insights into the homeostatic mechanisms governing multiclonal T cell populations.
  • The human immune system maintains a vast and dynamic repertoire of T cell clonotypes, with significant overlap between clonotypes and naive T cells.