THE MOUSE MAMMARY-TUMOR VIRUS ENV GENE IS THE SOURCE OF A CD8(-CELL-STIMULATING PEPTIDE PRESENTED BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE IN A MURINE THYMOMA() T)
S. Malarkannan et al., THE MOUSE MAMMARY-TUMOR VIRUS ENV GENE IS THE SOURCE OF A CD8(-CELL-STIMULATING PEPTIDE PRESENTED BY A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE IN A MURINE THYMOMA() T), Proceedings of the National Academy of Sciences of the United Statesof America, 93(24), 1996, pp. 13991-13996
CD8(+) cytotoxic T cells recognize their targets by the presence of un
ique peptide bound to a major histocompatibility complex (ME-IC) class
I molecules on the cell surface. The MHC molecules normally display t
housands of distinct peptides, making it difficult to identify individ
ual antigenic peptides, their protein precursors, and their relative i
mportance in the T-cell response. sere 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 libr
ary, These expression screens allowed identification of a mouse mammar
y tumor virus (MMTV) transcript as the source of the antigenic peptide
presented by the K-b 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 concentr
ations and coeluted with one of two active peptides in HPLC-fractionat
ed extracts of EL-4 cells. The AFV8/K-b complex was also recognized by
two other EL-4-specific T cells. The results illustrate a novel strat
egy for identifying T-cell-stimulating antigens and suggest that the M
MTV env gene and its naturally processed AFV8 peptide product can serv
e as a model for study of antigen processing and tumor immunotherapy.