Multiplicity of virus-encoded helper T-cell epitopes expressed on FBL-3 tumor cells.
To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper cell clones were isolated from C57BL/6 mice and the fourth was isolated from a (BALB/c x C57BL/6)F1 mouse. All these clones proliferated in response to the immunizing FBL-3 tumor cells in a major histocompatibility complex class II-restricted manner. Each clone expressed a distinct T-cell receptor with a characteristic combination of alpha and beta chains. The localization of helper T-cell determinants on viral proteins was analyzed with recombinant vaccinia viruses expressing Friend murine leukemia virus (F-MuLV) gag or env genes or shorter fragments of the env gene. Epitopes recognized by these T-cell clones were mapped to at least two distinct portions in the env region of the F-MuLV genome. These epitopes were identified more precisely with synthetic peptides derived from the F-MuLV envelope protein sequence. One of these epitopes was common to Friend and Moloney MuLVs and was located in the N-terminal region of the gp70 glycoprotein at amino acids 122 to 141. The second epitope, which was recognized in the context of hybrid I-Eb/d major histocompatibility complex class II molecule, was located close to the C-terminal end of gp70 at amino acids 462 to 479. In addition, a possible third epitope was located in the N-terminal half of the gp70 sequence and differed from the first epitope in that it was not cross-reactive with the Moloney MuLV envelope protein.
Iwashiro
M
M
Institute for Immunology, Faculty of Medicine, Kyoto University, Japan.
Kondo
T
T
Shimizu
T
T
Yamagishi
H
H
Takahashi
K
K
Matsubayashi
Y
Y
Masuda
T
T
Otaka
A
A
Fujii
N
N
Ishimoto
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002999:Clone Cells; D003433:Crosses, Genetic; D000939:Epitopes / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005622:Friend murine leukemia virus / Q000235:genetics*; D015686:Gene Products, env / Q000276:immunology; D015752:Genes, env; D007942:Leukemia, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D015183:Restriction Mapping; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000939:Epitopes; D015686:Gene Products, env; D016693:Receptors, Antigen, T-Cell, alpha-beta