Junctional sequences influence the specificity of γ/δ T cell receptors

Abstract

T lymphocytes bearing the γ/δ T cell receptor (TCR-γ/δ) express a limited number of germline variable gene segments, generating receptor sequence diversity primarily through junctional mechanisms. To examine the role of V(D)J junctional sequences in antigen recognition by TCR-γ/δ, we derived an alloreactive murine TCR-γ/δ+ T cell line, LKD1, specific for the I-Ad class II major histocompatibility complex (MHC) molecule, and compared its receptor with that expressed by a previously characterized class II MHC alloreactive T cell line, LBK5, specific for I-Ek,b,s la molecules. Both LKD1 and LBK5 express receptors encoded by rearranged Vγ1.2Jγ2 and Vδ5Dδ2Jδ1 gene elements, differing in sequence only in the V(D)J junctional regions of the γ and δ genes. These results demonstrate that junctionally encoded sequences corresponding to the putative third complementarity determining region can influence the antigen specificity of TCR-γ/δ.