Molecular cloning of sheep T cell receptor γ and δ chain constant regions: unusual primary structure of γ chain hinge segments

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Abstract
The primary structure of sheep T cell receptor (TcR) γ and δ chain constant (C) regions has been determined by cDNA cloning. A comparison of the nucleotide and deduced amino acid sequences of the sheep chains with known human and mouse sequences shows that the primary structure of the immunoglobulin, transmembrane and cytoplasmic Cγ domains and all of the Cδ region has been substantially conserved. However, the hinge or connector region of sheep γ chains differs significantly from all known TcR chains. Clones representing two different sheep Cγ genes were isolated and both contain additional sequence in this region, making them the longest TcR chains so far identified. The hinge region of both sheep Cγ sequences contains two additional cysteine residues and a motif of five amino acids (TTESP or TTEPP) which has been triplicated in one of the clones. Other repetitive segments of 13–17 amino acids could also be identified suggesting that, as in the human Cγ2 gene, this region of the sheep genes could have arisen from an exon duplication or triplication event. Southern blot analysis of sheep DNA confirmed the presence of one Cδ gene and at least two Cγgenes. A restriction fragment length polymorphism that is probably associated with allelic sequence variation in the sheep Cδ gene was detected in DNA from different animals. Although the essential structure of the γ/δ TcR appears well conserved through evolution, the marked heterogeneity evident in the hinge region of γ chains both within and between species, and particularly the presence of additional cysteine residues in the sheep sequences, may be of structural and functional importance.