Recognition of envelope protein by dengue virus serotype-specific human CD4+ CD8- cytotoxic T-cell clones.
We analyzed dengue virus-specific CD4+ CD8- cytotoxic T lymphocytes (CTL) at the clonal level to further understand their role in dengue virus infections. Stimulation of peripheral blood mononuclear cells from two dengue virus type 4 (D4V)-immune donors with live D4V or noninfectious D4V antigen generated 17 HLA class II-restricted CD4+ CTL capable of specific lysis of dengue virus antigen-treated autologous lymphoblastoid cell lines. Thirteen clones were D4V specific, three clones were cross-reactive for D2V and D4V, and one clone was cross-reactive for D1V, D3V, and D4V. Antigen recognition by six D4V-specific clones and three D2V- and D4V-cross-reactive clones was restricted by HLA-DR7. Five D4V-specific CD4+ CTL clones lysed autologous lymphoblastoid cell lines infected with a dengue virus-vaccinia virus recombinant containing the E gene of D4V, whereas three serotype-cross-reactive CTL clones did not. These results indicate that E-specific clones are serotype specific and HLA-DR7 restricted in these two donors and suggest that a common epitope on E protein may be recognized. E protein-specific CD4+ CTL may be important mediators of virus clearance especially during reinfection with the same serotype as that in primary infection by providing help for virus-specific antibody production and lysis of virus-infected cells.
Livingston
P G
PG
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Kurane
I
I
Lai
C J
CJ
Bray
M
M
Ennis
F A
FA
D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002999:Clone Cells; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D003715:Dengue / Q000517:prevention & control; D003716:Dengue Virus / Q000145:classification / Q000276:immunology*; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D007114:Immunization; D012703:Serotyping; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000956:Antigens, Viral; D016827:CD8 Antigens; D015809:HLA-DR7 Antigen; D014759:Viral Envelope Proteins