Overlapping epitopes of friend murine leukemia virus gag-encoded leader sequence recognized by single cytotoxic T-lymphocyte clones.
The leader signal sequence of the non-structural gag-encoded glycoprotein precursor, Pr75gag, of Friend murine leukemia virus (F-MuLV) contains overlapping epitopes, SIVLCCLCL (p71-79) and CCLCLTVFL (p75 83) that activate Friend virus (FV)-induced tumor (FBL-3)-specific cytotoxic T-lymphocytes (CTL) (Kondo et al., J. Virol., 69, 1995, 6735-6741; Chen et al., J. Virol., 70, 1996, 7773-7782). It was investigated whether these two peptides are recognized by a single CTL clone or by individual clones with different specificities. The results show that both hydrophobic and cysteine-containing peptides are bound to H-2Db class I major histocompatibility complex (MHC) molecules and cross-recognized by a single CTL clone as well as bulk-cultured CTL from the spleens of mice immunized with FBL-3. The peptide p71-79 was effective for sensitizing target cells to lysis by CTL in the concentration of common antigenic peptides. Moreover, peptide p75-83 was 1000-fold more potent than the peptide p71-79. Specific cytotoxicity assays with variant peptides with alanine- and serine-substitutions suggested a highly complex function of the disulfide bond-forming peptides potentially sensitive to small sequence differences. The dominance of CTL responses to the transmembrane region is discussed in light of the high affinity of a novel hydrophobic peptide to compete with other peptides for binding to MHC molecules.
Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
H
H
Uenishi
N
N
Iwanami
K
K
Kuribayashi
H
H
Tamamura
N
N
Fujii
T
T
Nakatani
T
T
Kawasaki
H
H
Yamagishi
D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005622:Friend murine leukemia virus / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D021382:Protein Sorting Signals