Identification of a second major tumor-specific antigen recognized by CTLson mouse mastocytoma P815

Murine mastocytoma P815 induces CTL responses against at least four distinc t Ags (AB, C, D, and E), Recent studies have shown that the main component of the CTL response against the P815 tumor is targeted against Ags P815AB a nd P815E, The gene PIA has been well characterized, It encodes the P815AB A g in the form of a nonameric peptide containing two epitopes, P815A and P81 5B, which are recognized by different CTLs. Here, we report the identificat ion of the P815E Ag, Using a cDNA library derived from tumor P815, we ident ified the gene coding for P815E. We also characterized the antigenic peptid e that anti-P815E CTLs recognize on the MHC class I molecule H-2K(d), The P 815E Ag results from a mutation within an ubiquitously expressed gene encod ing methionine sulfoxide reductase, an enzyme that is believed to be import ant in the protection of proteins against the by-products of aerobic metabo lism Surprisingly, immunizing mice i.p. with syngeneic tumor cells (L1210) that were constructed to express B7-1 and P815E did not induce resistance a gainst live P815, even though a strong anti-P815E CTL response was observed with splenocytes from immunized animals.