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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.
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Generation of Discriminative Human Monoclonal Antibodies from Rare Antigen-specific B Cells Circulating in Blood

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Engineering Antibodies Targeting p16 MHC-Peptide Complexes.

Nicholas J Rettko¹, Judith Campisi^2,3, James A Wells^1,4

¹Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California 94158, United States.

ACS Chemical Biology

|February 25, 2022

Summary

Researchers identified a novel way to target senescent cells, which contribute to aging. They developed antibodies that recognize a specific protein (p16) on these cells, offering a potential new strategy for senolytic therapies.

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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes

A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes

Published on: March 25, 2014

Area of Science:

Immunology
Cell Biology
Gerontology

Background:

Senescent cells permanently arrest cell division and contribute to age-related diseases.
Eliminating senescent cells expressing p16^Ink4a (p16) in mice increases lifespan and delays aging.
Targeting native human senescent cells expressing p16 remains a significant challenge.

Purpose of the Study:

To investigate if senescent cells display p16-derived peptides in major histocompatibility complex (MHC)-peptide complexes on their surface.
To develop antibody-based biologics targeting these unique cell surface antigens for senolytic therapy.

Main Methods:

Utilized Fab-phage display technology to generate antibodies against p16 MHC-peptide complexes.
Created antibodies targeting p16 MHC-peptide complexes associated with HLA-B*35:01 and HLA-A*02:01 alleles.
Engineered single-chain Fab chimeric antigen receptor (CAR) constructs from generated antibodies.

Main Results:

Successfully generated antibodies that bind to p16 MHC-peptide complexes on specific human leukocyte antigen (HLA) alleles.
Demonstrated that CAR constructs can recognize naturally presented p16 MHC-peptide complexes on target cells.
Showed activation of Jurkat cells upon recognition of these senescent cell surface antigens.

Conclusions:

Senescent cells present p16-derived peptides within MHC-peptide complexes on their surface, serving as potential targetable antigens.
Developed a platform for surveying senescent cells using novel antibodies.
Established a potential new senolytic strategy targeting p16-expressing senescent cells via antibody-based biologics.