Mutation of human immunodeficiency virus type 1 at amino acid 585 on gp41 results in loss of killing by CD8+ A24-restricted cytotoxic T lymphocytes.
A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at amino acid 585 which is present in some prototype human immunodeficiency virus type 1 strains, e.g., ADA, JFL, SC, ALA1, BAL1, SF2, VRF, SF33, and WMJ2. This finding that a mutation at amino acid 585 on gp41 results in nonrecognition by human leukocyte antigen A24-restricted CD8+ cytotoxic T lymphocytes suggests that antigenic variation at T-cell epitopes contributes to the failure of immune control of human immunodeficiency virus type 1 infections.
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655.
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Dai
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West
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Littaua
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Takahashi
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Ennis
D000595:Amino Acid Sequence; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005822:Genetic Vectors; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D000943:Antigens, Differentiation; D016827:CD8 Antigens; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D015234:HLA-A Antigens; D010446:Peptide Fragments