Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α. (1st January 2023)

• Record Type: Journal Article
• Authors: Zhou, Chao-Ying; Wang, Rui-Ning; He, Wen-Ting; Luo, Dong-Rong; Yuan, Si-Rui; Wen, Qian; Hu, Sheng-Feng; Zhou, Xin-Ying; Ma, Li
• Is Part Of: AIDS. Volume 37:Number 1(2023)
• Page Start: 33
• Page End: 42
• Publication Date: 2023-01-01
• Subjects: adoptive cellular immunotherapy -- alanine substitution -- bispecific T-cell receptor -- complementarity determining region 3α -- Mycobacterium tuberculosis/HIV coinfection; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000003408
• Languages: English
• ISSNs: 0269-9370

Abstract

Abstract : 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 Ag85B199–207 and HIV-1 Env120–128 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 especially important for antigen recognition. These results will pave the way for the future development of an improved high-affinity bispecific TCR for use in adoptive cellular immunotherapy for MTB/HIV coinfected patients.