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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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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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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.
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Updated: Jun 3, 2025

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Modifications to rhesus macaque TCR constant regions improve TCR cell surface expression.

Lori V Coren1, Matthew T Trivett1, Jorden L Welker1

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Optimizing T cell receptor (TCR) constructs in rhesus macaque models enhances surface expression. Murinization of constant regions significantly boosts TCR expression, crucial for cellular immunotherapy development.

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Area of Science:

  • Immunology
  • Cellular Therapy
  • Biotechnology

Background:

  • T cell immunotherapy efficacy relies on sufficient surface antigen receptor expression on engineered cells.
  • Challenges include optimizing engineering, coding sequences, and preventing mispairing of exogenous and endogenous T cell receptor (TCR) chains.
  • Preclinical models are vital for refining engineering designs and assessing safety.

Purpose of the Study:

  • To enhance rhesus macaque T cell receptor (TCR) surface expression in primary cells for improved TCR-based cellular immunotherapy models.
  • To evaluate five alternative TCRαβ constant region constructs for their impact on surface expression and function.

Main Methods:

  • Generated five distinct TCRαβ constant region constructs for a SIV Gag-specific TCR in rhesus macaque primary cells.
  • Constructs included human codon-optimized rhesus macaque TCR, disulfide linkage, minimal murine substitutions, full murinization, and murinization with FG loop modification.
  • Assessed surface expression levels and cytokine production upon antigen-specific stimulation.

Main Results:

  • Murinization or minimal amino acid substitutions to the constant region significantly increased rhesus macaque TCR surface expression compared to wild-type.
  • All engineered TCR constructs maintained their ability to induce cytokine production in response to cognate peptide antigen stimulation.
  • Specific modifications, particularly murinization, proved most effective in enhancing surface expression.

Conclusions:

  • Modifications to the TCR constant region, especially murinization, are effective strategies for increasing surface TCR expression in rhesus macaque models.
  • These optimized TCR constructs retain antigen-specific functionality, supporting their use in preclinical immunotherapy studies.
  • Findings inform the design of TCRs for advanced rhesus macaque models of TCR-based cellular immunotherapy.