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.
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
A
A
Hosmalin
M
M
Clerici
R
R
Houghten
C D
CD
Pendleton
C
C
Flexner
D R
DR
Lucey
B
B
Moss
R N
RN
Germain
G M
GM
Shearer
J A
JA
Berzofsky
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