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Related Concept Videos

Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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 reactivity.
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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...
Antigen Processing Pathways01:31

Antigen Processing Pathways

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...
Cross-reactivity00:42

Cross-reactivity

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Personalized Peptide Arrays for Detection of HLA Alloantibodies in Organ Transplantation
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A generalizable system for antigenic peptide targeting across HLA-I allotypes.

Wyatt Blackson1, Ean L Small2, Shirley M Sun2,3

  • 1Department of Chemical Engineering, Stanford University, Stanford, CA, USA.

Biorxiv : the Preprint Server for Biology
|June 4, 2026
PubMed
Summary

Researchers developed a new immunotherapy approach using engineered binders (xTRACeRs) that work across diverse Human Leucocyte Antigen (HLA) types. This expands potential patient coverage for targeted cancer therapies by overcoming HLA restrictions.

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Published on: March 25, 2014

Area of Science:

  • Immunology and Cancer Therapeutics
  • Protein Engineering and Structural Biology

Background:

  • T cell receptors (TCRs) and TCR-mimicking antibodies target peptide antigens presented by Human Leucocyte Antigen (HLA-I) molecules.
  • HLA polymorphism presents a major hurdle for developing broadly applicable immunotherapies, limiting coverage across diverse patient genetic backgrounds.
  • Existing therapeutic modalities struggle to address the molecular diversity of HLA proteins and peptide antigens.

Purpose of the Study:

  • To develop a generalized framework for engineering cross-HLA compatible binders (xTRACeRs) that maintain peptide specificity.
  • To overcome the limitations imposed by HLA allotype diversity in the development of targeted immunotherapies.

Main Methods:

  • Combined a peptide conformational prediction tool (PepPred) with a cross-HLA binding protein engineering system (TRACeR-I).
  • Developed and validated xTRACeRs against clinically relevant peptide antigens across common alleles within five HLA-A/B/C supertypes.
  • Utilized Cryo-electron microscopy (Cryo-EM) to determine the structural basis of xTRACeR-peptide-HLA complexes.

Main Results:

  • Successfully developed xTRACeRs demonstrating compatibility across different HLA allotypes while maintaining high peptide specificity.
  • Cryo-EM structures revealed mechanisms by which xTRACeRs navigate polymorphic HLA residues and interact with peptide antigens (e.g., PRAME, PHOX2B).
  • Engineered xTRACeRs, when implemented as Chimeric Antigen Receptor (CAR) T cells, showed potent and specific tumor cell killing efficacy.

Conclusions:

  • The developed framework provides a generalized approach to create binders effective across diverse HLA supertypes.
  • Overcoming HLA supertype restriction significantly expands patient coverage for HLA-targeted immunotherapies.
  • This strategy holds promise for advancing the development of more inclusive and effective cancer treatments.