Cross-reactive lysis of human targets infected with prototypic and clinical human immunodeficiency virus type 1 (HIV-1) strains by murine anti-HIV-1 IIIB env-specific cytotoxic T lymphocytes.
To evaluate the ability of murine anti-human immunodeficiency virus type 1 (HIV-1) IIIB env cytotoxic T lymphocytes (CTL) to recognize and lyse HIV-1-infected cells, we have constructed a human cell line (Hu/Dd) expressing both the CD4 receptor and the murine H-2Dd major histocompatibility complex (MHC) class I protein. This cell line can be productively infected with HIV-1 and can also function as a target for murine CD8+, class I MHC-restricted CTL directed against the envelope glycoprotein of HIV-1 IIIB. The ability of BALB/c anti-HIV-1 IIIB env CTL to specifically recognize and lyse Hu/Dd target cells infected with divergent HIV-1 strains was tested by using both prototypic and clinical HIV-1 strains. CTL generated by immunization of mice with syngeneic cells expressing either the native or V3 loop-deleted (delta V3) envelope glycoprotein from HIV-1 IIIB were able to recognize and specifically lyse Hu/Dd target cells infected with the HIV-1 prototypic isolates IIIB, MN, WMJ II, SF2, and CC as well as several HIV-1 clinical isolates. These results demonstrate that CTL determinants for HIV-1 env exist outside the hypervariable V3 region, anti-HIV-1 IIIB env CTL appear to recognize common determinants on diverse HIV-1 strains, and classification of HIV-1 strains based on neutralizing antibody reactivities does not appear to correspond to CTL recognition and lysis. The results suggest that the cell-mediated components of the immune system may have a broader recognition of divergent HIV-1 strains than do the humoral components.
Department of Molecular Virology, Viagene Inc., San Diego, California 92121.
S
S
Chada
C E
CE
DeJesus
K
K
Townsend
W T
WT
Lee
L
L
Laube
D J
DJ
Jolly
S M
SM
Chang
J F
JF
Warner
D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D005805:Genes, MHC Class I / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017384:Sequence Deletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014616:Vaccinia virus / Q000235:genetics
D016827:CD8 Antigens; D015686:Gene Products, env