Induction of cross-reactivity in an endogenous viral peptide non-reactive to FBL-3 tumor-specific helper T-cell clones.
We previously reported a helper T-cell (Th) epitope (peptide i) which corresponded to the sequence ranging from positions 462 to 479 from the N-terminus of the Friend-murine leukemia virus (F-MuLV) envelope protein (env462-479). Homologous sequences exist in both Moloney-murine leukemia (M-MuLV env452-469) and endogenous AKV (AKV env453-470) viruses, which differ from F-MuLV env462-479 in 5 and 7 amino acids, respectively. However, peptide i-specific Th clones did not respond to either of the corresponding exogenous or endogenous peptides. One amino acid substitution in M-MuLV env452-469 (Asn to Tyr at position 465: N465Y) and three amino acids in AKV env453-470 (H460S, A466Y and Y468H) endowed both peptides with the reactivity to one of the Th clones, F5-5, almost to the same degree as peptide i. However, the other Th clones responded differently to each of the modified endogenous peptides substituted by one to three amino acids. The cells responsive to the cross-reactive peptides occupied only a minor portion, if any, of the bulk cultured lymph node cells from peptide i-immune mice, and in particular, no significant response to the modified endogenous peptides was observed in repeated experiments. The exchange of at least 3 residues was necessary for the endogenous peptide to acquire sufficient cross-reactivity to two of the three Th clones. However, it was noticeable that a single substitution of alanine by tyrosine at the dominant T-cell receptor (TCR) contact position of the peptide i(e) generated a weak but significant cross-reactivity to one of the three Th clones in this study. Thus, peptides of endogenous retroviral origin that would be modified by mutational events might become 'non-self' and prime Th cells leading to auto-antibody production and resulting in autoimmune disease.
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan.
H
H
Uenishi
N
N
Iwanami
H
H
Yamagishi
T
T
Nakatani
T
T
Kawasaki
H
H
Tamamura
N
N
Fujii
K
K
Kuribayashi
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000276:immunology; D002999:Clone Cells; D003429:Cross Reactions; D003433:Crosses, Genetic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005622:Friend murine leukemia virus / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000276:immunology; D016415:Sequence Alignment; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env