The TCR β-chain constant region stabilizes the αβ heterodimer and facilitates interactions with CD3 signaling complexes (CD3δε, CD3γε, and CD3ζζ) . Key functions include:
Signal transduction: Mediates intracellular signaling via immunoreceptor tyrosine-based activation motifs (ITAMs) in CD3 subunits .
Thymic selection: Public TCR β-chains (e.g., B6.2.16β) show conserved use across individuals, suggesting preferential pairing with diverse α-chains during thymic selection .
Peripheral survival: Some β-chains enhance T-cell survival through interactions with self-peptide/MHC complexes .
The B6.2.16β chain (Vβ8.2-Jβ2.3) dominates anti-Smcy responses in mice, appearing in 5/5 individuals despite differing α-chains .
Public β-chains like GDNSAETL exhibit minimal N-region diversity, suggesting recombination bias .
Cysteine mutagenesis (e.g., Thr48→Cys in Cα, Ser57→Cys in Cβ) promotes disulfide bonding, increasing matched αβ pairing by 95% compared to wild-type .
Modified β-chains show 3–5× higher surface expression in transfected T cells .
Single-cell PCR revealed that ancestral β-chain rearrangements generate "half-sibling" T cells with identical β-chains but diverse α-chains .
Example: A β-chain cohort from anti-tumor responses paired with distinct CDR3α loops (Jα45, Jα12) .
The B6.2.16β chain dominated D<sup>b</sup>-Smcy-specific responses in mice immunized with DNA vaccines, confirming its conserved role across antigen delivery methods .
Engineered β-chains with cysteine pairs reduce mismatched TCR pairing risks, improving safety in adoptive T-cell therapies .