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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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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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An observation that illustrates most T cell receptor structure-function relationships.

Melvin Cohn1

  • 1Conceptual Immunology Group, The Salk Institute, 10010 N. Torrey Pines Rd, La Jolla, CA, 92037, USA. cohn@salk.edu.

Immunologic Research
|October 20, 2017
PubMed
Summary
This summary is machine-generated.

The standard model of T cell receptor (TCR) structure-function relationships is challenged by new analysis. A competing framework better explains TCR recognition of peptide-presenting molecules and alloreactivity.

Keywords:
AlloreactivityRestrictive recognition of peptideSignalingStructure-function relationshipsTCR

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Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • The standard model of T cell receptor (TCR) structure-function relationships is based on an analogy with B cell receptors.
  • This model faces challenges in explaining specific aspects of TCR recognition, including allele-specific interactions and alloreactivity.

Purpose of the Study:

  • To analyze a key observation that challenges the standard model of TCR structure-function relationships.
  • To present and discuss a competing framework for understanding TCR function.

Main Methods:

  • Analysis of a single key observation regarding TCR recognition.
  • Conceptual comparison of the standard model with a competing framework.

Main Results:

  • The standard model is shown to be untenable for explaining allele-specific recognition of MHC-encoded peptide presenters (R) by TCR.
  • The standard model inadequately explains TCR alloreactivity.
  • A competing framework is proposed, positing single V-domains for R allele recognition, peptide-specific restrictive reactivity, peptide-unspecific alloreactivity, and TCRs existing in two reciprocal conformations.

Conclusions:

  • Competing conceptualizations are crucial for advancing experimentation and creative thinking in TCR research.
  • The proposed competing framework offers a potentially more robust explanation for TCR structure-function relationships than the standard model.