Key result
Sequencing of 68 HLA-DQ2.5-glia-α2-specific T cells from coeliac disease patients showed over-usage of the TRBV7-2 gene segment and strict usage of TRAV26-1 in clones with the canonical TCRβ chain.
Observational (n=68)
The study identifies specific biased TCRα and TCRβ chain pairings in gluten-specific T cells in coeliac disease, providing insights into the molecular basis of antigen recognition.
Reinforces TCR bias observations in coeliac disease; leaves open targeted therapies pending validation.
CD4⁺ T cells that recognize dietary gluten antigens presented by the disease-associated HLA-DQ2 or DQ8 molecules are central players in coeliac disease. Unbiased sequencing of the human TCRα variable (TRAV) and humanTCRβ variable (TRBV) genes of 68 HLA-DQ2.5-glia-α2-specific T cells from coeliac disease patients confirmed previous reports of over-usage of the TRBV7-2 gene segment, a conserved Arg residue in the complementarity-determining region (CDR) 3β loop and prevalent usage of the canonical ASSxRxTDTQY CDR3β loop among T cells with this specificity. In 30 clones that had the canonical TCRβ chain, we found a strict usage of the TRAV26-1 gene segment in the TCRα chain. There was variable usage of the TRAJ genes and diverse CDR3α sequences with no apparent conserved motifs. This study extends previous reports on biased TCR usage in both HLA-DQ2.5- and DQ8-restricted gluten-specific TCRs and provides data for further studies on TRAV and TRBV pairing.
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Qiao et al. (2013) conducted an observational in Coeliac disease (n=68). HLA-DQ2.5-glia-α2-specific T cells was evaluated on TCRα and TCRβ gene usage. Sequencing of 68 HLA-DQ2.5-glia-α2-specific T cells from coeliac disease patients showed over-usage of the TRBV7-2 gene segment and strict usage of TRAV26-1 in clones with the canonical TCRβ chain.
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