Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein.
A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr----Val or Thr----Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection.
Takahashi
K
K
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
Dai
L C
LC
Fuerst
T R
TR
Biddison
W E
WE
Earl
P L
PL
Moss
B
B
Ennis
F A
FA
D000595:Amino Acid Sequence; D016827:CD8 Antigens / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D015234:HLA-A Antigens / Q000276:immunology*; D015791:HLA-A3 Antigen; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D016827:CD8 Antigens; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D015234:HLA-A Antigens; C071694:HLA-A*03:01:01:01 antigen; D015791:HLA-A3 Antigen; D046911:Macromolecular Substances; D010455:Peptides; D014759:Viral Envelope Proteins