Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two different serotype specificities

• Published in: The Journal of immunology (1950) Vol. 154; no. 3; pp. 1287 - 1295
• Main Authors: Livingston, PG, Kurane, I, Dai, LC, Okamoto, Y, Lai, CJ, Men, R, Karaki, S, Takiguchi, M, Ennis, FA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.02.1995
• Subjects: Adult; Amino Acid Sequence; Animals; Antigens, Viral - immunology; Cell Line; Cytotoxicity Tests, Immunologic; Dengue Virus - classification; Dengue Virus - immunology; Epitopes - immunology; HLA-B35 Antigen - genetics; HLA-B35 Antigen - immunology; Humans; L Cells (Cell Line); Mice; Molecular Sequence Data; Receptors, Antigen, T-Cell - genetics; RNA Helicases; Serine Endopeptidases; Serotyping; T-Lymphocytes, Cytotoxic - immunology; Transfection; Viral Nonstructural Proteins - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.154.3.1287

Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. We analyzed dengue virus-specific CD8+ CD4- CTL at the clonal level to further understand the role of CD8+ CTL in dengue virus infections. Dengue virus-specific CD8+ CTL clones were established from lymphocytes of a dengue 4-immune adult. Three patterns of dengue serotype specificities were identified: 1) specific for dengue 4, 2) cross-reactive for dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four dengue virus serotypes. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone were further analyzed. All four of the clones were HLA-B35 restricted and recognized NS3. The epitopes were mapped to amino acids (aa) 483 to 618 of NS3. The epitope was then defined by using synthetic peptides. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone recognized the same peptide (TPEGIIPTL) encompassing aa 500 to 508 of dengue 4 NS3. The peptide encompassing aa 500-508 of dengue 2 NS3 was recognized by a dengue 2/dengue 4 cross-reactive clone but was not recognized by the dengue 4-specific clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clones used different TCR. These results indicate that CD8+ CTL clones that use different TCR and demonstrate two distinct serotype specificities recognize the same 9-mer peptide in the context of HLA-B35.