PMID- 36979478 OWN - NLM STAT- MEDLINE DCOM- 20230330 LR - 20230331 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 13 IP - 3 DP - 2023 Mar 16 TI - 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. LID - 10.3390/biom13030545 [doi] LID - 545 AB - 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-gamma 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 Tax(11-19) 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 Tax(11-19). On the other hand, Tax(11-19) 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-gamma-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 Tax(11-19), for the rational design of immunomodulatory strategies for HTLV-1 chronic diseases. FAU - Pereira-Santos, Thaiza Aline AU - Pereira-Santos TA AUID- ORCID: 0000-0002-8661-6599 AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - da Rocha, Anderson Santos AU - da Rocha AS AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - Lopes-Ribeiro, Agata AU - Lopes-Ribeiro A AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - Correa-Dias, Laura Cardoso AU - Correa-Dias LC AUID- ORCID: 0000-0002-8286-7083 AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - Melo-Oliveira, Patricia AU - Melo-Oliveira P AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - Reis, Erik Vinicius de Sousa AU - Reis EVS AUID- ORCID: 0000-0001-5442-6240 AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - da Fonseca, Flavio Guimaraes AU - da Fonseca FG AUID- ORCID: 0000-0002-1416-8694 AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. AD - Centro de Tecnologia em Vacinas (CT-Vacinas), Parque Tecnologico de Belo Horizonte, Belo Horizonte 31310-260, MG, Brazil. FAU - Barbosa-Stancioli, Edel Figueiredo AU - Barbosa-Stancioli EF AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. FAU - Tsuji, Moriya AU - Tsuji M AUID- ORCID: 0000-0001-8587-277X AD - Aaron Diamond AIDS Research Center, Division of Infectious Disease, Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA. FAU - Coelho-Dos-Reis, Jordana Grazziela Alves AU - Coelho-Dos-Reis JGA AUID- ORCID: 0000-0002-2360-1875 AD - Laboratorio de Virologia Basica e Aplicada (LVBA), Departamento de Microbiologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230316 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (HLA-A2 Antigen) RN - 0 (Immunodominant Epitopes) RN - 0 (Gene Products, tax) RN - 207137-56-2 (Interleukin-4) RN - 0 (Peptides) SB - IM MH - Humans MH - *Human T-lymphotropic virus 1/genetics MH - HLA-A2 Antigen MH - Immunodominant Epitopes MH - Gene Products, tax/genetics MH - T-Lymphocytes, Cytotoxic MH - Interleukin-4 MH - Peptides PMC - PMC10046496 OTO - NOTNLM OT - CD8+ T-cell response OT - HLA-A2 haplotype OT - HTLV-1 OT - MHC-I peptides OT - Tax OT - immunodominance OT - immunoinformatics COIS- The authors declare no conflict of interest. EDAT- 2023/03/30 06:00 MHDA- 2023/03/30 06:11 PMCR- 2023/03/16 CRDT- 2023/03/29 01:19 PHST- 2022/12/15 00:00 [received] PHST- 2023/02/09 00:00 [revised] PHST- 2023/02/24 00:00 [accepted] PHST- 2023/03/30 06:11 [medline] PHST- 2023/03/29 01:19 [entrez] PHST- 2023/03/30 06:00 [pubmed] PHST- 2023/03/16 00:00 [pmc-release] AID - biom13030545 [pii] AID - biomolecules-13-00545 [pii] AID - 10.3390/biom13030545 [doi] PST - epublish SO - Biomolecules. 2023 Mar 16;13(3):545. doi: 10.3390/biom13030545.