Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α

作者：Chaoying Zhou, Ruining Wang, Wenting He, Dong-Rong Luo, Si-Rui Yuan, Qian Wen, Sheng-Feng Hu, Xinying Zhou, Ma Li · 发表于：AIDS · 年份：2022 · DOI：10.1097/qad.0000000000003408 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Monoclonal and Polyclonal Antibodies Research、Immune Cell Function and Interaction

OBJECTIVE: Mycobacterium tuberculosis /human immunodeficiency virus (MTB/HIV) coinfection has become an urgent problem in the field of prevention and control of infectious diseases in recent years. Adoptive cellular immunotherapy using antigen-specific T-cell receptor (TCR) engineered T cells which recognize the specific antigen artificially may have tremendous potential in anti-MTB/HIV coinfection. We have previously successfully identified a MTB Ag85B 199-207 and HIV-1 Env 120-128 peptide-bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A∗0201 + healthy individual and have further studied that how residues on the predicted complementarity determining region (CDR) 3 of the β chain contribute to the bispecific TCR contact with the peptide-MHC. However, it is not clear which amino acids in the predicted CDR3α of the bispecific TCR play a crucial role in ligand recognition. METHODS: The variants in the CDR3α of the bispecific TCR were generated using alanine substitution. We then evaluated the immune effects of the five variants on T-cell recognition upon encounter with the MTB or HIV-1 antigen. RESULTS: Mutation of two amino acids (E112A, Y115A) in CDR3α of the bispecific TCR caused a markedly diminished T-cell response to antigen, whereas mutation of the other three amino acids (S113A, P114A, S116A) resulted in completely eliminated response. CONCLUSION: This study demonstrates that Ser 113 , Pro 114 and Ser 116 in CDR3α of the bispecific TCR are e...