Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen.
Journal
  Cancer research.
Citation
  Cancer Res. 61(3):873-9
Publication date
  2001 Feb 1
Authors
  Schell TD
Lippolis JD
Tevethia SS
Investigators
  Todd Schell
Satvir S. Tevethia
Grant agencies
  National Cancer Institute
Grants
  NCI R37 CA25000
MeSH headings
  Antigens, Polyomavirus Transforming
Antigens, Viral, Tumor
Epitopes, T-Lymphocyte
HLA-A2 Antigen
T-Lymphocytes, Cytotoxic
MeSH qualifiers
  immunology
Abstract
  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.
Medline ID
  21115809