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Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α
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 th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794127/ https://www.ncbi.nlm.nih.gov/pubmed/36281689 http://dx.doi.org/10.1097/QAD.0000000000003408 |
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author | 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 |
author_facet | 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 |
author_sort | Zhou, Chao-Ying |
collection | PubMed |
description | 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 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. |
format | Online Article Text |
id | pubmed-9794127 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-97941272023-01-04 Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α 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 AIDS Basic Science 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 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. Lippincott Williams & Wilkins 2023-01-01 2022-10-18 /pmc/articles/PMC9794127/ /pubmed/36281689 http://dx.doi.org/10.1097/QAD.0000000000003408 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
spellingShingle | Basic Science 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 Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title | Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title_full | Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title_fullStr | Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title_full_unstemmed | Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title_short | Functional analysis of the antigen binding sites on the MTB/HIV-1 peptide bispecific T-cell receptor complementarity determining region 3α |
title_sort | functional analysis of the antigen binding sites on the mtb/hiv-1 peptide bispecific t-cell receptor complementarity determining region 3α |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794127/ https://www.ncbi.nlm.nih.gov/pubmed/36281689 http://dx.doi.org/10.1097/QAD.0000000000003408 |
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