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 glycoprot ein precursor, pr75(gag), of Friend murine leukemia virus (F-MuLV) con tains overlapping epitopes, SIVLCCLCL (p71-79) and CCLCLTVFL (p75-83) that activate Friend virus (FV)-induced tumor (FBL-3)-specific cytotox ic T-lymphocytes (CTL) (Kondo et al., J. Virol., 69, 1995, 6735-6741; Chen et al., J. Virol., 70, 1996, 7773-7782). It was investigated whet her these two peptides are recognized by a single CTL clone or by indi vidual clones with different specificities. The results show that both hydrophobic and cysteine-containing peptides are bound to H-2D(b) cla ss I major histocompatibility complex (MHC) molecules and cross-recogn ized by a single CTL clone as well as bulk-cultured CTL from the splee ns of mice immunized with FBL-3. The peptide p71-79 was effective for sensitizing target cells to lysis by CTL in the concentration of commo n antigenic peptides. Moreover, peptide p75-83 was 1000-fold more pote nt than the peptide p71-79. Specific cytotoxicity assays with variant peptides with alanine- and serine-substitutions suggested a highly com plex function of the disulfide bond-forming peptides potentially sensi tive 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 bindin g to MHC molecules. (C) 1998 Elsevier Science B.V. All rights reserved .