We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

Autoimmunity-Associated T Cell Receptors Recognize HLA-Variant-Bound Peptides

By LabMedica International staff writers
Posted on 13 Dec 2022
Print article
Image: A T cell receptor that recognizes a human protein fragment (left) is remarkably similar to one that recognizes a bacterial protein fragment (right), and to two receptors capable of recognizing both human and bacterial protein fragments (middle) (Photo courtesy of Washington University School of Medicine)
Image: A T cell receptor that recognizes a human protein fragment (left) is remarkably similar to one that recognizes a bacterial protein fragment (right), and to two receptors capable of recognizing both human and bacterial protein fragments (middle) (Photo courtesy of Washington University School of Medicine)

The immune response in autoimmune disease recapitulates that of responses directed against infection, except that self-antigens are, or become, the target of the adaptive immune system. These self-antigens may drive a process that is localized within a specific organ, such as the thyroid gland (Grave’s disease, Hashimoto’s thyroiditis) or brain (multiple sclerosis).

Autoimmune disease occurs when an immune response attacks one’s own tissues. Like all adaptive immune responses, it is focused on specific antigens by T-cell receptors and B-cell receptors. In contrast to infection, the antigens that these cells recognize are processed from proteins within the target organ and this drives a chronic inflammatory process that disrupts the normal function of the tissue.

A large international team of immunologists partially led by those at Washington University School of Medicine in St. Louis (St Louis, MO, USA) investigated the theory that some T cells that react to microbes also may react to normal human proteins, causing autoimmune disease. The autoimmune diseases ankylosing spondylitis, which involves arthritis in the spine and pelvis, and acute anterior uveitis, which is characterized by inflammation in the eye, are both strongly associated with an HLA variant called HLA-B*27.

The team devised a method to identify protein fragments that drive a T cell response when combined with HLA-B*27, and mapped the fragments against the human genome and five bacterial genomes to identify proteins from which the fragments may have originated. They isolated orphan T cell receptors (TCRs) expressing a disease-associated public β-chain variable region–complementary-determining region 3β (BV9–CDR3β) motif2,3,4 from blood and synovial fluid T cells from individuals with ankylosing spondylitis (AS) and from the eye in individuals with acute anterior uveitis (AAU).

These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. The investigators used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide–MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9–CDR3β TCRs.

Michael Paley, MD, PhD, an Assistant Professor of Medicine and a co-author of the study, said, “For ankylosing spondylitis, the average time between initial symptoms and actual diagnosis is seven to eight years. Shortening that time with improved diagnostics could make a dramatic impact on patients' lives, because treatment could be initiated earlier. As for therapeutics, if we could target these disease-causing T cells for elimination, we could potentially cure a patient or maybe even prevent the disease in people with the high-risk genetic variant. There's a lot of potential for clinical benefit here.” The study was published on December 7, 2022 in the journal Nature.

Related Links:
Washington University School of Medicine

HLX
New
Platinum Supplier
ADAMTS-13 Protease Activity Test
ATS-13 Activity Assay
New
Diagnostic Salivary DHEA ELISA Kit
Salimetrics Salivary DHEA Enzyme Immunoassay Kit
New
SARS-CoV-2 Test
BioCode SARS-CoV-2 Assay

Print article

Channels

Clinical Chem.

view channel
Image: Electrochemical cells etched by laser on wooden tongue depressor measure glucose and nitrite in saliva (Photo courtesy of Analytical Chemistry)

Biosensor-Fabricated Wooden Tongue Depressor Measures Glucose and Nitrite in Saliva

Physicians often use tongue depressors to examine a patient's mouth and throat. However, it is hard to imagine that this simple wooden tool could actively assess a patient's health. This idea has led to... Read more

Molecular Diagnostics

view channel
Image: The Geo portable testing platform integrated with the Snap collection device (Photo courtesy of ReadyGo Diagnostics)

Ultra-Portable Rapid Test Platform Offers Complete Sample-to-Answer Solution for Remote and Off-Grid Testing

An ultra-portable isothermal molecular diagnostics system integrated with a patented device which combines sample collection and processing into a single, easy-to-use disposable is set to revolutionize... Read more

Hematology

view channel
Image: The Atellica HEMA 570 and 580 hematology analyzers remove workflow barriers (Photo courtesy of Siemens)

Next-Gen Hematology Analyzers Eliminate Workflow Roadblocks and Achieve Fast Throughput

Hematology testing is a critical aspect of patient care, utilized to establish a patient's health baseline, track treatment progress, or guide timely modifications to care. However, increasing constraints... Read more

Microbiology

view channel
Image: The rapid MTB strip test for tuberculosis can identify TB patients within two hours (Photo courtesy of Chulalongkorn University)

Rapid MTB Strip Test Detects Tuberculosis in Less Than an Hour without Special Tools

Tuberculosis (TB), a highly infectious disease, continues to pose significant challenges to public health worldwide. TB is caused by a bacterium known as "Mycobacterium tuberculosis," spreading through... Read more

Pathology

view channel
Image: The UNIQO 160 (CE-IVDR) advances diagnostic analysis for autoimmune diseases (Photo courtesy of EUROIMMUN)

Novel Automated IIFT System Enables Cutting-Edge Diagnostic Analysis

A newly-launched automated indirect immunofluorescence test (IIFT) system for autoimmune disease diagnostics offers an all-in-one solution to enhance the efficiency of the complete IIFT process, comprising... Read more

Technology

view channel
Electronic biosensor uses DNA aptamers for detecting biomarkers in whole blood samples (Photo courtesy of Freepik)

Electronic Biosensor Detects Biomarkers in Whole Blood Samples without Addition of Reagents

The absence of robust, reliable, and user-friendly bioanalytical tools for early and timely diagnosis of cardiovascular diseases, particularly sudden cardiac arrest, leads to preventable deaths and imposes... Read more

Industry

view channel
Image: The global HbA1c testing devices market is expected to reach USD 2.56 billion in 2027 (Photo courtesy of Freepik)

Global Hemoglobin A1c Testing Devices Market Driven by Rising Prevalence of Diabetes

Hemoglobin A1c (HbA1c), or glycated hemoglobin, refers to hemoglobin with glucose attached. HbA1c testing devices are used for blood tests that determine average blood glucose, or blood sugar levels.... Read more
Copyright © 2000-2023 Globetech Media. All rights reserved.