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Related Concept Videos

Antigen Processing Pathways01:31

Antigen Processing Pathways

932
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
932
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

455
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
Complete antigens possess both immunogenicity and...
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

658
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

Diversity of Antigen Receptors

519
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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Related Experiment Video

Updated: Jun 5, 2025

Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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A general system for targeting MHC class II-antigen complex via a single adaptable loop.

Haotian Du1, Jingjia Liu2, Kevin M Jude3

  • 1Department of Chemistry, Stanford University, Stanford, CA, USA.

Nature Biotechnology
|December 13, 2024
PubMed
Summary
This summary is machine-generated.

We developed TRACeR-II, a novel method for rapidly creating peptide-specific binders targeting Major Histocompatibility Complex class II (MHCII) molecules. This approach offers a versatile platform for developing new therapies for autoimmune diseases.

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Area of Science:

  • Immunology
  • Structural Biology
  • Protein Engineering

Background:

  • Major histocompatibility complex class II (MHCII) molecules present peptide antigens to CD4+ T cells, crucial for immune responses.
  • Targeting peptide-MHCII complexes with T cell receptors (TCRs) or TCR-like antibodies shows therapeutic potential for autoimmune diseases and microbiome tolerance.

Purpose of the Study:

  • To introduce a general and rapid method, TRACeR-II, for developing peptide-specific MHCII binders.
  • To create versatile binders with a small scaffold and single recognition loop for targeting diverse MHCII antigens.

Main Methods:

  • Development of targeted recognition of antigen-MHC complex reporter for MHCII (TRACeR-II) binders.
  • Utilizing a small helical bundle scaffold with a single recognition loop for peptide-MHCII interaction.
  • Employing computational protein design for in silico generation of specific binding sequences.

Main Results:

  • Demonstrated rapid generation of TRACeR-II binders with affinities in the low-nanomolar to low-micromolar range.
  • Achieved binding affinities comparable to established TCRs and antibodies.
  • Successfully designed specific binding sequences computationally from a SARS-CoV-2 peptide sequence.

Conclusions:

  • TRACeR-II offers a straightforward and versatile approach for targeting antigen-MHCII complexes.
  • This method bypasses the need for combinatorial selection on complementarity-determining region loops.
  • TRACeR-II facilitates the development of novel therapeutics for immune-related conditions.