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Detection of autoreactive CD4+ T cells by MHC class II multimers in HLA-linked human autoimmune diseases
Karolin Wieber, … , Christine L. Zimmer, Michael Hertl
Karolin Wieber, … , Christine L. Zimmer, Michael Hertl
Published May 3, 2021
Citation Information: J Clin Invest. 2021;131(9):e148674. https://doi.org/10.1172/JCI148674.
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Commentary

Detection of autoreactive CD4+ T cells by MHC class II multimers in HLA-linked human autoimmune diseases

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Abstract

Recognition of self-peptides in association with distinct HLA class II alleles by autoreactive CD4+ T cells is central for loss of immunological tolerance leading to autoimmune disease. However, identifying immunodominant self-peptides and characterizing autoreactive T cells is challenging. In this issue of the JCI, Falta et al. identify a disease-associated complementarity-determining region 3β motif specific for beryllium-modified C-C motif ligand 4 (CCL4) and CCL3 self-peptides in patients with chronic beryllium disease (CBD), a granulomatous lung disorder with a known HLA class II allelic association. Detection of these antigen-specific CD4+ T cells by beryllium-pulsed HLA-DP2 tetramers presenting CCL4/CCL3 confirms these autoantigens in humans and mice and enables monitoring in the progress of disease. Detection of autoreactive CD4+ T cells by peptide–MHC class II multimers allows for the detailed characterization of disease-promoting T cells. This knowledge has profound implications for the monitoring and development of targeted therapies in human autoimmune disorders.

Authors

Karolin Wieber, Christine L. Zimmer, Michael Hertl

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Figure 1

pMHC multimer technology can reveal HLA class II–restricted, autoreactive CD4+ T cells in human autoimmune disorders.

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pMHC multimer technology can reveal HLA class II–restricted, autoreactiv...
(A) Autoimmune diseases with known HLA association and identified immunogenic self-peptides enable the study of autoreactive CD4+ T cells by pMHC multimers. (B) Available multimeric pMHC complexes can detect autoreactive CD4+ T cells in CBD and PV. In CBD (left), CCL4/CCL3-reactive effector T cells promote inflammation. In PV (right), Dsg3-reactive T cells help B cells with autoantibody production.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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