Autoimmune susceptibility imposed by public TCRβ chains

Area of Science:

• Immunology
• Autoimmunity
• T-cell biology

Background:

• T-cell receptors (TCRs) are crucial for adaptive immunity, recognizing antigens.
• A subset of TCR chains, termed public TCRs, are shared among individuals and implicated in autoimmunity.
• The role of public TCRβ chains in modulating T-cell responses to autoantigens remains unclear.

Purpose of the Study:

• To investigate whether public TCRβ chains confer reactivity to autoantigens.
• To determine if public TCRβ chains influence autoimmune disease development.
• To explore the potential of public TCR sequences as biomarkers or therapeutic targets.

Main Methods:

• Utilized transgenic expression of public and private TCRβ chains from autoimmune encephalomyelitis-associated TCRs.
• Assessed autoantigen reactivity in unprimed T cells expressing specific TCRβ chains paired with endogenous TCRα.
• Evaluated spontaneous autoimmunity in mice harboring transgenic TCRβ chains.

Main Results:

• Transgenic expression of public TCRβ, but not private TCRβ, conferred autoantigen reactivity to T cells.
• Two of six public TCRβ chains induced spontaneous early-onset autoimmunity in mice, while none of the private TCRβ chains did.
• Single TCRβ chains were sufficient to direct TCRαβ heterodimer reactivity towards disease-associated autoantigens.

Conclusions:

• Public TCRβ chains can confer reactivity to autoantigens and influence autoimmune susceptibility.
• Specific public TCR sequences may serve as biomarkers for autoimmune diseases.
• Targeting public TCRs presents a potential therapeutic strategy for autoimmune conditions.