Structural and biophysical insights into the TCRαβ complex in chickens

Summary In this work, chicken HPAIV H5N1-epitope-specific TCRαβ (ch-TCRαβ) was isolated, and its structure was determined. The Cα domain of ch-TCRαβ does not exhibit the typical structure of human TCRαβ, and the DE loop extends outward, resulting in close proximity between the Cα domain of ch-TCRαβ and CD3eδ/γ. The FG loop of the Cβ domain of ch-TCRαβ is shorter. The changes in the C domains of ch-TCRαβ and the difference in chicken CD3eδ/γ confirm that the complexes formed by TCRαβ and CD3eδ/γ differ from those in humans. In the chicken complex, a positively charged cleft is formed between the two CDR3 loops that might accommodate the acidic side chains of the chicken pMHC-I-bound HPAIV-epitope intermediate portion oriented towards ch-TCRαβ. This is the first reported structure of chicken TCRαβ, and it provides a structural model of the ancestral TCR system in the immune synapses between T-cells and antigen-presenting cells in lower vertebrates.