The mouse mammary tumor virus env gene is the source of a CD8+ T-cell-stimulating peptide presented by a major histocompatibility complex class I molecule in a murine thymoma. Proc Natl Acad Sci U S A 1996 Nov 26;93(24):13991-6
Date
11/26/1996Pubmed ID
8943048Pubmed Central ID
PMC19482DOI
10.1073/pnas.93.24.13991Scopus ID
2-s2.0-0030475228 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
CD8+ cytotoxic T cells recognize their targets by the presence of unique peptide bound to a major histocompatibility complex (MHC) class I molecules on the cell surface. The MHC molecules normally display thousands of distinct peptides, making it difficult to identify individual antigenic peptides, their protein precursors, and their relative importance in the T-cell response. Here we used the EL-4 tumor-specific lacZ-inducible KZ30.6 T cell as a probe for detecting the peptide/MHC ligand that was generated in cells transfected with an EL-4 cDNA library. These expression screens allowed identification of a mouse mammary tumor virus (MMTV) transcript as the source of the antigenic peptide presented by the Kb MHC molecule. The antigenic activity was encoded within the MMTV env gene and was defined by the octapeptide ANYDFICV (AFV8). Synthetic AFV8 stimulated KZ30.6 T cells at picomolar concentrations and coeluted with one of two active peptides in HPLC-fractionated extracts of EL-4 cells. The AFV8/Kb complex was also recognized by two other EL-4-specific T cells. The results illustrate a novel strategy for identifying T-cell-stimulating antigens and suggest that the MMTV env gene and its naturally processed AFV8 peptide product can serve as a model for study of antigen processing and tumor immunotherapy.
Author List
Malarkannan S, Serwold T, Nguyen V, Sherman LA, Shastri NAuthor
Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
CD8-Positive T-Lymphocytes
COS Cells
Cloning, Molecular
Gene Library
Gene Products, env
Genes, env
H-2 Antigens
Mammary Tumor Virus, Mouse
Mice
Mice, Inbred Strains
Oligopeptides
Recombinant Proteins
Thymoma
Thymus Neoplasms
Transcription, Genetic
Transfection
Tumor Cells, Cultured
