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A6242 - Cell-based Comprehensive and Systematic Binding Analysis Between HLA -DR or -DQ Regions and T Cell Epitopes of TB Antigens
Author Block: Y. Hoshino1, H. Miyadera2, H. Nagai3, T. Yoshiyama4, K. Tokunaga5; 1National Institute of Infectious Diseases, Tokyo, Japan, 2University of Tsukuba, Tsukuba, Japan, 3National Hospital Organization, Tokyo National Hospital, Tokyo, Japan, 4Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan, 5The University of Tokyo, Tokyo, Japan.
Rationale: Host immune responses toward Mycobacterium tuberculosis (TB) include T cell responses to RD1 locus antigens such as CFP-10/ESAT-6. To elucidate the precise mechanism of this interaction and involvement with the association of HLA genotype, we inferred T cell epitopes on CFP-10/ESAT-6 from combination with HLA class II typing assay and immune cell analysis by ELISPOT in tuberculosis patients (J. Immunol. Res. 2014 ). In the present study, we develop large scale and cell-based analysis to evaluate interactions between T cell epitope regions on CFP-10/ESAT-6 and allele products on HLA-DRB1/3/4/5 or -DQ to reveal how TB epitopes on T cells were restricted by HLA class II molecules.
Methods: We previously estimated interactions between HLA class II and peptide through cell-based assay, which used HLA class II beta chain fused with a sequence that encodes peptide (J. Clin. Invest. 2015). In the present study, we extended this assay to analyze interactions between representative DR and DQ molecules encoded on representative HLA-DR-DQ haplotypes and are potentially involved in presentations of CFP-10/ESAT-6-derived T-cell epitopes.
Results and Conclusion: We chose 14 types of HLA-DRB1/3/4/5 and 7 types of HLA-DQ that were frequently recognized in Japanese tuberculosis patients and assayed with 9 dominant types of TB T cell epitope regions. Based on these data, we speculate HLA DR- and DQ- alleles that can strongly present TB T cell epitopes.