CD8+ T cell Recognition of Polymorphic Wild Type Sequence p53 65–73 Peptides in Squamous Cell Carcinoma of the Head and Neck

The HLA‐A*0201‐restricted wt peptide, p53 65–73 , encompasses a well‐studied polymorphism in TP53, at codon 72 (R/P), which is homozygous (R/R) in over half of the world population. In vitro stimulation of PBMC from healthy donors led to the generation of wt p53 65–73 ‐specific CD8+ T cells in a substantial number of individuals. Generation of CTL recognizing either p53 65–73 P or p53 65–73 R, after IVS of PBMC from homozygous or heterozygous donors was successful, and recognition of either allelic peptide was observed, regardless of the genotype of the donor T cells or the peptide used as a target. HLA A*0201+ tumor cell lines which are either homozygous (R/R or P/P) or heterozygous (R/P) at codon 72, demonstrated cross‐recognition by a panel of p53 65–73 ‐specific CTL. More efficient HLA‐A*0201 binding was observed with the p53 65–73 P versus the p53 65–73 R allelic peptide, indicating that p53 65–73 P variant peptide could be useful as an enhanced epitope for vaccine application. However, we found preferential recognition of p53 65–73 R expressing target cells, regardless of the allelic peptide used to generate in IVS cultures. In addition, since p53 homozygosity (R/R) is widely prevalent, this enables vaccination with the nonself p53 65–73 P, peptide avoiding self tolerance and future thymic deletion and may permit the utilization of p53 65–73 P to most efficiently target this epitope in wt p53‐based vaccines.