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Biomolecules
Volume 13
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10.3390/biom13030545
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Article

Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions

by
Thaiza Aline Pereira-Santos
1,
Anderson Santos da Rocha
1,
Ágata Lopes-Ribeiro
1,
Laura Cardoso Corrêa-Dias
1,
Patrícia Melo-Oliveira
1,
Erik Vinicius de Sousa Reis
1,
Flávio Guimarães da Fonseca
1,2,
Edel Figueiredo Barbosa-Stancioli
1,
Moriya Tsuji
3 and
Jordana Grazziela Alves Coelho-dos-Reis
1,*
1
Laboratório de Virologia Básica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
2
Centro de Tecnologia em Vacinas (CT-Vacinas), Parque Tecnológico de Belo Horizonte, Belo Horizonte 31310-260, MG, Brazil
3
Aaron Diamond AIDS Research Center, Division of Infectious Disease, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
Biomolecules 2023, 13(3), 545; https://doi.org/10.3390/biom13030545
Submission received: 15 December 2022 / Revised: 9 February 2023 / Accepted: 24 February 2023 / Published: 16 March 2023
(This article belongs to the Special Issue Innovative Immunology: A Themed Issue Dedicated to Professor Moriya Tsuji)
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Abstract

The present study sought to search for the immunodominance related to the N-terminal, Central and C-terminal regions of HTLV-1 Tax using novel, cutting-edge peptide microarray analysis. In addition, in silico predictions were performed to verify the presence of nine amino acid peptides present along Tax restricted to the human leukocyte antigen (HLA)-A2.02*01 haplotype, as well as to verify the ability to induce pro-inflammatory and regulatory cytokines, such as IFN-γ and IL-4, respectively. Our results indicated abundant dose-dependent reactivity for HLA-A*02:01 in all regions (N-terminal, Central and C-terminal), but with specific hotspots. Furthermore, the results of fold-change over the Tax11–19 reactivity obtained at lower concentrations of HLA-A*02:01 reveal that peptides from the three regions contain sequences that react 100 times more than Tax11–19. On the other hand, Tax11–19 has similar or superior HLA-A*02:01 reactivity at higher concentrations of this haplotype. The in silico analysis showed a higher frequency of IFN-γ-inducing peptides in the N-terminal portion, while the C-terminal portion showed a higher frequency of IL-4 inducers. Taken together, these results shed light on the search for new Tax immunodominant epitopes, in addition to the canonic Tax11–19, for the rational design of immunomodulatory strategies for HTLV-1 chronic diseases.
Keywords: HTLV-1; Tax; MHC-I peptides; CD8+ T-cell response; HLA-A2 haplotype; immunoinformatics; immunodominance HTLV-1; Tax; MHC-I peptides; CD8+ T-cell response; HLA-A2 haplotype; immunoinformatics; immunodominance
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MDPI and ACS Style

Pereira-Santos, T.A.; da Rocha, A.S.; Lopes-Ribeiro, Á.; Corrêa-Dias, L.C.; Melo-Oliveira, P.; Reis, E.V.d.S.; da Fonseca, F.G.; Barbosa-Stancioli, E.F.; Tsuji, M.; Coelho-dos-Reis, J.G.A. Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions. Biomolecules 2023, 13, 545. https://doi.org/10.3390/biom13030545

AMA Style

Pereira-Santos TA, da Rocha AS, Lopes-Ribeiro Á, Corrêa-Dias LC, Melo-Oliveira P, Reis EVdS, da Fonseca FG, Barbosa-Stancioli EF, Tsuji M, Coelho-dos-Reis JGA. Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions. Biomolecules. 2023; 13(3):545. https://doi.org/10.3390/biom13030545

Chicago/Turabian Style

Pereira-Santos, Thaiza Aline, Anderson Santos da Rocha, Ágata Lopes-Ribeiro, Laura Cardoso Corrêa-Dias, Patrícia Melo-Oliveira, Erik Vinicius de Sousa Reis, Flávio Guimarães da Fonseca, Edel Figueiredo Barbosa-Stancioli, Moriya Tsuji, and Jordana Grazziela Alves Coelho-dos-Reis. 2023. "Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions" Biomolecules 13, no. 3: 545. https://doi.org/10.3390/biom13030545

APA Style

Pereira-Santos, T. A., da Rocha, A. S., Lopes-Ribeiro, Á., Corrêa-Dias, L. C., Melo-Oliveira, P., Reis, E. V. d. S., da Fonseca, F. G., Barbosa-Stancioli, E. F., Tsuji, M., & Coelho-dos-Reis, J. G. A. (2023). Diversity of HLA-A2-Restricted and Immunodominant Epitope Repertoire of Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Protein: Novel Insights among N-Terminal, Central and C-Terminal Regions. Biomolecules, 13(3), 545. https://doi.org/10.3390/biom13030545

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