Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen.
Recent reports have documented the presence of SV40 large T antigen (T ag) sequences in a number of human tumors and raised the question of whether cellular immunity to T ag is elicited in such individuals. We used HLA-A2.1 transgenic C57BL/6 mice to identify an epitope from T ag recognized by CD8+ CTLs when presented by this human MHC class I molecule. Immunization of HLA-A2.1 transgenic mice with syngeneic T ag-transformed cells resulted in the induction of HLA-A2.1-restricted, T ag-specific CTLs. The target epitope, residues 281-289 (KCDDVLLLL) of T ag, was identified using both cell lines expressing T ag variants and synthetic T ag peptides. Peptide 281-289 bound stably to HLA-A2.1 molecules, effectively sensitized target cells for CTL lysis, and was efficiently processed from endogenous T ag in cells of both mouse and human origin. CTLs were not cross-reactive on the human BK or JC virus T ags. Thus, SV40 T ag 281-289 represents a potential specific CTL recognition epitope for humans.
Schell
T D
TD
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Lippolis
J D
JD
Tevethia
S S
SS
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000276:immunology*; D002460:Cell Line; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology; D013539:Simian virus 40 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000952:Antigens, Polyomavirus Transforming; D000957:Antigens, Viral, Tumor; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments