Viral antigen mismatch affects antiviral T-cell response and may impair immunotherapeutic efficacy against ATL
Abstract Human T-cell leukemia virus type 1 (HTLV-1) has the potential to transform primary CD4+T cellsin vitrowithin a short time; however, the majority of infected individuals maintain an asymptomatic and disease-free condition, suggesting the existence of an equilibrium between the proliferation of infected cells and host immunity. The decline in anti-viral immunity contributes to the transformation of the infected cells, leading to the development of adult T-cell leukemia/lymphoma (ATL). This study identified a variation in a major viral antigen, HTLV-1 Tax, in human leukocyte antigen-A24 (HLA-A24) positive individuals. Two variants of Tax301-309peptides, SFHNLHLLF (Tax301-309A) and SFHSLHLLF (Tax301-309B) were found to induce distinct T-cell immune responses in HLA-A24 positive individuals. There was a disparity between two Tax301-309peptides in the detection of anti-Tax301-309cytotoxic T-lymphocytes (CTLs) binding to A24/peptide multimers by flow cytometry analysis. More importantly, over half of the anti-Tax TCRs of anti-Tax CTLs from infected individuals did not recognize mismatched Tax301-309peptides by Enzyme-Linked Immunospot (ELISpot) assay using Jurkat T cells expressing the anti-Tax301-309specific TCR. These findings underscore the importance of matching the viral antigen epitope type in T-cell-based immunotherapy against ATL by using viral antigen Tax.Key points <jats:list list-type="bullet">Epitope heterogeneity in the major viral antigen in HTLV-1 infection causes different T-cell responses in infected individuals.Recommended guideline; performing virus typing to obtain optimal efficacy in T-cell-mediated immunotherapy against the viral antigen Tax.
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 31. Jan. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sugata, Kenji [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
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| doi: |
10.1101/2024.01.25.576615 |
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| PPN (Katalog-ID): |
XBI042320534 |
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| 245 | 1 | 0 | |a Viral antigen mismatch affects antiviral T-cell response and may impair immunotherapeutic efficacy against ATL |
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| 520 | |a Abstract Human T-cell leukemia virus type 1 (HTLV-1) has the potential to transform primary CD4+T cellsin vitrowithin a short time; however, the majority of infected individuals maintain an asymptomatic and disease-free condition, suggesting the existence of an equilibrium between the proliferation of infected cells and host immunity. The decline in anti-viral immunity contributes to the transformation of the infected cells, leading to the development of adult T-cell leukemia/lymphoma (ATL). This study identified a variation in a major viral antigen, HTLV-1 Tax, in human leukocyte antigen-A24 (HLA-A24) positive individuals. Two variants of Tax301-309peptides, SFHNLHLLF (Tax301-309A) and SFHSLHLLF (Tax301-309B) were found to induce distinct T-cell immune responses in HLA-A24 positive individuals. There was a disparity between two Tax301-309peptides in the detection of anti-Tax301-309cytotoxic T-lymphocytes (CTLs) binding to A24/peptide multimers by flow cytometry analysis. More importantly, over half of the anti-Tax TCRs of anti-Tax CTLs from infected individuals did not recognize mismatched Tax301-309peptides by Enzyme-Linked Immunospot (ELISpot) assay using Jurkat T cells expressing the anti-Tax301-309specific TCR. These findings underscore the importance of matching the viral antigen epitope type in T-cell-based immunotherapy against ATL by using viral antigen Tax.Key points <jats:list list-type="bullet">Epitope heterogeneity in the major viral antigen in HTLV-1 infection causes different T-cell responses in infected individuals.Recommended guideline; performing virus typing to obtain optimal efficacy in T-cell-mediated immunotherapy against the viral antigen Tax | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Takatori, Mitsuyoshi |4 aut | |
| 700 | 1 | |a Reda, Omnia |0 (orcid)0000-0002-1260-0527 |4 aut | |
| 700 | 1 | |a Yang Tan, Benjy Jek |4 aut | |
| 700 | 1 | |a Tokunaga, Masahito |4 aut | |
| 700 | 1 | |a Sato, Tomoo |4 aut | |
| 700 | 1 | |a Ueda, Mitsuharu |0 (orcid)0000-0002-6814-0582 |4 aut | |
| 700 | 1 | |a Yamano, Yoshihisa |4 aut | |
| 700 | 1 | |a Utsunomiya, Atae |4 aut | |
| 700 | 1 | |a Satou, Yorifumi |0 (orcid)0000-0002-1495-7810 |4 aut | |
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