4.8 Review

Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.706136

Keywords

adaptive immunity; immune equilibrium; T-cell receptor repertoire; B-cell receptor repertoire; antigen presentation/recognition; homeostatic proliferation; a rank-size frequency distribution of T; and B-cell receptors; immunopeptidome

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Funding

  1. Russian Science Foundation [21-65-00004]
  2. Russian Science Foundation [21-65-00004] Funding Source: Russian Science Foundation

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The structure and organization of antigen-recognizing repertoires of B and T cells play a crucial role in immune equilibrium and protection. Alterations in these landscapes, such as changes in HLA gene variants and presenting antigen spectra, can impact immune function and contribute to the development of oncological and autoimmune diseases. Understanding the mechanisms behind these changes is essential for managing the risk associated with immune system sensitivity to infectious agents.
In this review, we described the structure and organization of antigen-recognizing repertoires of B and T cells from the standpoint of modern immunology. We summarized the latest advances in bioinformatics analysis of sequencing data from T and B cell repertoires and also presented contemporary ideas about the mechanisms of clonal diversity formation at different stages of organism development. At the same time, we focused on the importance of the allelic variants of the HLA genes and spectra of presented antigens for the formation of T-cell receptors (TCR) landscapes. The main idea of this review is that immune equilibrium and proper functioning of immunity are highly dependent on the interaction between the recognition and the presentation landscapes of antigens. Certain changes in these landscapes can occur during life, which can affect the protective function of adaptive immunity. We described some mechanisms associated with these changes, for example, the conversion of effector cells into regulatory cells and vice versa due to the trans-differentiation or bystander effect, changes in the clonal organization of the general TCR repertoire due to homeostatic proliferation or aging, and the background for the altered presentation of some antigens due to SNP mutations of MHC, or the alteration of the presenting antigens due to post-translational modifications. The authors suggest that such alterations can lead to an increase in the risk of the development of oncological and autoimmune diseases and influence the sensitivity of the organism to different infectious agents.

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