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Antigens Involved in Adaptive Immunity

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...

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Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay

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Deep mapping of the TCR-antigen interface using pMHC-pseudotyped viruses and yeast display.

Stephanie A Gaglione, Jonathan Krog, Frances R Keer

Biorxiv : the Preprint Server for Biology

|September 5, 2025

Summary

VelociRAPTR, a new method, rapidly screens millions of T cell receptor (TCR) interactions with antigens. It maps how TCR sequences influence antigen recognition, aiding T cell therapy development and predicting off-target effects.

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Last Updated: May 6, 2026

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Published on: October 30, 2015

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Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs

Published on: September 10, 2017

Area of Science:

Immunology
Molecular Biology
Biotechnology

Background:

T cell receptor (TCR) specificity is crucial for effective T cell therapies.
Current methods for mapping TCR-antigen interactions lack scalability.
Understanding TCR sequence-function relationships is vital for therapeutic development.

Purpose of the Study:

To develop a scalable method for mapping TCR specificity against diverse antigens.
To investigate how TCR sequence variations, particularly in CDR3 loops, affect antigen recognition.
To generate deep, high-throughput data on TCR-antigen interactions for engineering and predictive modeling.

Main Methods:

Introduction of VelociRAPTR, a library-on-library screening approach.
Utilizing yeast-displayed TCR libraries and peptide-MHC displaying virus-like particles (pMHC-VLPs).
Simultaneous screening of millions of TCR variants against multiple pMHCs, including mutations in CDR3 loops and peptides.

Main Results:

pMHC-VLPs demonstrated efficient binding to yeast-displayed TCRs, yielding data comparable to recombinant pMHC proteins.
VelociRAPTR successfully screened 47 million TCR variants against 92 pMHCs.
Generated detailed CDR3-pMHC maps revealing how CDR3 loop mutations modulate specificity, enabling selective constraint or broadening of recognition.

Conclusions:

VelociRAPTR provides a generalizable strategy for high-throughput protein-protein interaction mapping.
The generated maps offer insights for engineering TCRs with tailored pMHC binding profiles.
This approach enhances models for predicting TCR-antigen interactions and off-target recognition in T cell therapies.