An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type 1 gag.
A unique epitope on the gag protein of human immunodeficiency virus type 1 (HIV-1), located at amino acid 145 to 150, has been mapped by using a CD8+ cytotoxic T-lymphocyte (CTL) clone. This epitope is highly conserved among 18 HIV-1 strains. The HIV-1 gag-specific human leukocyte antigen (HLA) class I-restricted CD8+ CTL clone was generated from fresh peripheral blood mononuclear cells of an HIV-seropositive donor by stimulation with gamma-irradiated allogeneic peripheral blood mononuclear cells in the presence of an anti-CD3 monoclonal antibody and recombinant interleukin-2. This gag-specific CTL clone killed autologous target cells infected with a recombinant vaccinia virus containing the gag gene of HIV-1 and target cells pulsed with an authentic p24gag construct expressed in Escherichia coli. Fine specificity was determined by using a panel of overlapping 30-amino-acid-long synthetic peptides and subsequently using smaller peptides to precisely map the CTL domain on p24. The epitope is on a highly conserved region, and it overlaps with a major B-cell epitope of gag. This CD8+ T-cell epitope is restricted by HLA-Cw3, which has not been previously identified as a restricting element for human CTL responses.
Littaua
R A
RA
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Oldstone
M B
MB
Takeda
A
A
Debouck
C
C
Wong
J T
JT
Tuazon
C U
CU
Moss
B
B
Kievits
F
F
Ennis
F A
FA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016827:CD8 Antigens; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D000939:Epitopes; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D014758:Viral Core Proteins