Major and minor Kb-restricted epitopes encoded by the endogenous ecotropic murine leukemia virus AKR623 that are recognized by anti-AKR/Gross MuLV CTL.
C57BL/6 mice can generate a type-specific and class IH-2Kb-restricted CTL response against histocompatible AKR/Gross murine leukemia virus (MuLV) cell surface antigen positive (GCSA+) tumor cells. These anti-AKR/Gross MuLV CTL are also known to lyse SC.Kb/623 target cells expressing the molecular MuLV clone AKR623 (derived from the endogenous ecotropic MuLV provirus emv-11). To help identify AKR623 viral epitopes recognized by these CTL, four chimeric proviruses were constructed from two parental plasmids, pAKR623 and pAK7. It has been shown that SC.Kb/7 fibroblast targets expressing the emv-14-derived molecular clone AK7 are only poorly lysed by anti-AKR/Gross MuLV CTL. Data from experiments employing SC.Kb cells infected with the chimeras as targets against anti-AKR/Gross MuLV CTL supported the location of a previously identified immunodominant epitope located within the viral p15E transmembrane envelope protein, peptide TM134-141 (KSP-WFTTL). Furthermore, the use of Kb-motif-defined AKR623 encoded peptides together with data obtained using the chimeric viruses allowed the identification of three additional anti-AKR/Gross MuLV CTL epitopes. Peptides representing these epitopes, MA125-132 (RSALY-PAL), RT142-149 (SHRWYTVL), and RT456-463 (RMTHYQAM), are characterized herein with respect to their ability to confer lysis upon EMV- target cells and to stimulate tumor primed splenocytes in vitro. The identification and characterization of these additional epitopes allow for a better understanding of both the CTL response against GCSA+ tumor cells and the dysfunctional CTL response against EMV-14 and AK7.
Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire.
H D
HD
White
D A
DA
Roeder
T
T
Lam
W R
WR
Green
D000406:AKR murine leukemia virus / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000942:Antigens, Bacterial; D000954:Antigens, Surface / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology
D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D000956:Antigens, Viral; D016056:Immunodominant Epitopes; C030659:K antigens; D014759:Viral Envelope Proteins