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Pyruvate dehydrogenase specific T cells in primary biliary cirrhosis show restricted antigen recognition sites
Sabine Pingel1, Monika Arenz, Karl-Hermann Meyer zum Büschenfelde
1Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany.
Background/Aims:
The aim was to characterise the antigen recognition sites of the variable T cell receptor alpha-chain (TCRAV) and beta-chain (TCRBV) of T cells specific to the pyruvate dehydrogenase (PDC) in primary biliary cirrhosis.
Methods:
In 21 PDC-specific T cell clones isolated from five patients we analysed TCRAV and TCRBV usage by RT-PCR and sequenced the CDR3 regions.
Results:
Preferential expression of the TCR elements BV6 (6 clones), BV12 (4 clones) and BV1 (3 clones), and frequent usage of the joining elements JB2.3 and JB2.1 were seen. Analysis of the alpha chain revealed rearrangement of AV2 in 7 clones (35%) and AV7 in 3 clones, however, distribution of the joining elements was heterogenous and no common sequence motifs were detected. Evaluation of the physicochemical properties of the beta-chain demonstrated a positive charge at position P4 in several clones of two patients and a hydrophobic residue at position P5 in two different patients. Further, a conserved glycine at position P7 and neutral residues at positions P6 and P8 were frequently detected.
Conclusions:
Our data define TCR variable region restriction and preferred CDR3 features of PDC-specific T cells and support the notion that few relevant epitopes on the PDC complex are recognised by selected T cells.