An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes.
T-cell-mediated cytotoxicity may play an important role in control of infection by the human immunodeficiency virus (HIV). In this study, we have identified and characterized a relatively conserved epitope in the HIV-1 reverse transcriptase recognized by murine and human cytotoxic T cells. This epitope was identified using a murine antigen-specific CD8+ class I major histocompatibility complex-restricted cytotoxic T-cell (CTL) line, a transfected fibroblast cell line expressing the HIV-1 pol gene, recombinant vaccinia viruses containing different truncated versions of the pol gene, and overlapping synthetic peptides. The optimal antigenic site was identified as residues 203-219 by synthesizing extended or truncated peptide analogs of the antigenic fragment. The optimal peptide was then tested for sensitization of autologous Epstein-Barr virus-transformed B-cell targets for killing by fresh human peripheral blood mononuclear cells. It was recognized by CTLs from several HIV-seropositive patients but not from any seronegative donor. Therefore, this peptide is a good candidate for inclusion in an AIDS vaccine. This study demonstrates that the same CTL epitope can be seen by murine and human CD8+ CTLs, as previously demonstrated for epitopes recognized by CD4+ helper T cells, and suggests the utility of screening for immunodominant CTL epitopes in mice prior to carrying out studies in humans.
Hosmalin
A
A
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Clerici
M
M
Houghten
R
R
Pendleton
C D
CD
Flexner
C
C
Lucey
D R
DR
Moss
B
B
Germain
R N
RN
Shearer
G M
GM
Berzofsky
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000818:Animals; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis*; D015483:HIV Antibodies / Q000032:analysis; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D012194:RNA-Directed DNA Polymerase / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
D000939:Epitopes; D015483:HIV Antibodies; D012194:RNA-Directed DNA Polymerase