Plasticity of human CD8αα binding to peptide-HLA-A*2402

Abstract

The human CD8 functions as a co-receptor for specific T cell recognition, and only one complex structure of human CD8αα binding to HLA-A*0201 has been solved, revealing the molecular basis of CD8 interacting with its ligand pHLA. Here, we present the complex structures of human CD8αα bound to HLA-A*2402, which demonstrate two opposite α3 domain CD loop shifts (either pull or push) in the HLA heavy chain upon CD8 engagement. Taking the previously reported mouse CD8-pMHC complex structures into account, from the structural view, all of the data indicate the plasticity of CD8 binding to pMHC/HLA, which facilitates its co-receptor function for T cells. The plasticity of CD8 binding appears not to affect the specificity of TCR recognition, as no peptide conformation change extends to the pMHC interface for TCR contacting.