Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1.
The definition of human immunodeficiency virus type 1 (HIV-1) immunogenic epitopes is central to the rational design of AIDS vaccine strategies. In this study, we have generated seven HIV-1 reverse transcriptase-specific cytotoxic T-lymphocyte (CTL) clones from the peripheral blood of two seropositive subjects. Epitopes recognized by these CTL clones were identified by using target cells infected with recombinant HIV-1-vaccinia virus vectors expressing truncated reverse transcriptase proteins and further defined by using target cells incubated with overlapping 25-amino acid synthetic reverse transcriptase peptides. Five different CTL epitopes were identified, and in each case recognition was restricted by class I human leukocyte antigens (HLA). Clones maintained specific cytolytic function in continuous culture for up to 11 months, requiring only periodic restimulation with a CD3-specific monoclonal antibody. These results indicate that HIV-1-specific, major histocompatibility class I-restricted CTL recognize multiple epitopes of a single viral gene product in conjunction with different host HLA antigens. In addition, they demonstrate that human virus-specific CTL can be grown in long-term culture without the need for reexposure to viral antigen.
Walker
B D
BD
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Flexner
C
C
Birch-Limberger
K
K
Fisher
L
L
Paradis
T J
TJ
Aldovini
A
A
Young
R
R
Moss
B
B
Schooley
R T
RT
D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015870:Gene Expression; D005814:Genes, Viral; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics
D015678:Viral Structural Proteins; D012194:RNA-Directed DNA Polymerase