TY - JOUR
T1 - Antigen specificity of γδ T cells depends primarily on the flanking sequences of CDR3δ
AU - Xi, Xueyan
AU - Guo, Yang
AU - Chen, Hui
AU - Xu, Chunping
AU - Zhang, Huiyan
AU - Hu, Hongbu
AU - Cui, Lianxian
AU - Ba, Denian
AU - He, Wen
PY - 2009/10/2
Y1 - 2009/10/2
N2 - The structural basis that determines the specificity of γδ T cell receptor (TCR) recognition remains undefined. Our previous data show that the complementary determining region of human TCRδ (CDR3δ) is critical to ligand binding. Here we used linear and configurational approaches to examine the roles of V, N-D-N, or J regions in CDR3δ-mediated antigen recognition. Surprisingly, we found that the binding activities ofCDR3δ from different γδ TCRs to their target tissues and ligands depend on the conserved flanking sequences (V and J) but not as much on the D region of CDR3δ fragment. We further defined the key residues in the V and J regions of CDR3δ fragments, including the cysteine residue in the V fragment and the leucine residue in the J fragment that determine their ligand binding specificity. Our results demonstrate that TCRδ primarily uses conserved flanking regions to bind ligands. This finding may provide an explanation for the limited number of γδ TCR ligands that have as yet been identified.
AB - The structural basis that determines the specificity of γδ T cell receptor (TCR) recognition remains undefined. Our previous data show that the complementary determining region of human TCRδ (CDR3δ) is critical to ligand binding. Here we used linear and configurational approaches to examine the roles of V, N-D-N, or J regions in CDR3δ-mediated antigen recognition. Surprisingly, we found that the binding activities ofCDR3δ from different γδ TCRs to their target tissues and ligands depend on the conserved flanking sequences (V and J) but not as much on the D region of CDR3δ fragment. We further defined the key residues in the V and J regions of CDR3δ fragments, including the cysteine residue in the V fragment and the leucine residue in the J fragment that determine their ligand binding specificity. Our results demonstrate that TCRδ primarily uses conserved flanking regions to bind ligands. This finding may provide an explanation for the limited number of γδ TCR ligands that have as yet been identified.
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U2 - 10.1074/jbc.M109.011684
DO - 10.1074/jbc.M109.011684
M3 - Article
C2 - 19666468
AN - SCOPUS:70350444453
SN - 0021-9258
VL - 284
SP - 27449
EP - 27455
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -