DENGUE VIRUS-SPECIFIC, HLA-B35-RESTRICTED, HUMAN CD8(-LYMPHOCYTE (CTL) CLONES - RECOGNITION OF NS3 AMINO-ACID-500 TO AMINO-ACID-508 BY CTL CLONES OF 2 DIFFERENT SEROTYPE SPECIFICITIES() CYTOTOXIC T)

Dengue virus infections are a major cause of morbidity and mortality i n tropical and subtropical areas of the world. We analyzed dengue viru s-specific CD8(+) CD4(-) CTL at the clonal level to further understand the role of CD8(+) CTL in dengue virus infections. Dengue virus-speci fic CD8(+) CTL clones were established from lymphocytes of a dengue 4- immune adult. Three patterns of dengue serotype specificities were ide ntified: 1) specific for dengue 4, 2) cross-reactive for dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four den gue virus serotypes. Three dengue 4-specific clones and one dengue 2/d engue 4 cross-reactive clone were further analyzed. All four of the cl ones were HLA-B35 restricted and recognized NS3. The epitopes were map ped to amino acids (aa) 483 to 618 of NS3. The epitope was then define d by using synthetic peptides. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone recognized the same peptide (TP EGIIPTL) encompassing aa 500 to 508 of dengue 4 NS3. The peptide encom passing 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-specifi c clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clone s used different TCR. These results indicate that CD8(+) CTL clones th at use different TCR and demonstrate two distinct serotype specificiti es recognize the same 9-mer peptide in the context of HLA-B35.