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- Title
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.
- Authors
Pereira-Santos, Thaiza Aline; da Rocha, Anderson Santos; Lopes-Ribeiro, Ágata; Corrêa-Dias, Laura Cardoso; Melo-Oliveira, Patrícia; Reis, Erik Vinicius de Sousa; da Fonseca, Flávio Guimarães; Barbosa-Stancioli, Edel Figueiredo; Tsuji, Moriya; Coelho-dos-Reis, Jordana Grazziela Alves
- 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.
- Subjects
HTLV-I; SYNTAXINS; HLA histocompatibility antigens; HAPLOTYPES; PEPTIDES
- Publication
Biomolecules (2218-273X), 2023, Vol 13, Issue 3, p545
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom13030545