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Biomolecules, Vol. 13, Pages 545: 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 doi: 10.3390/biom13030545
Authors: Thaiza Aline Pereira-Santos 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 Jordana Grazziela Alves Coelho-dos-Reis
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.
