Binding of mutated Ras- and p53-derived peptides to HLA-DR molecules

We investigated binding of p53- and Ras-derived peptides with frequently observed missense mutations, to various L cell transfectants expressing a single species of HLA-DR complex, and found that: (i) all the synthetic peptides bound to various DR complexes with a variable affinity; (ii) some DR allelic products had a high affinity for both p53- and Ras-derived peptides (e.g., DRB1*1502), whereas others almost no affinity (e.g., DRB1*1101); and (iii) DR-binding motifs described in the literature can explain some of the allele-specific interactions between mutated peptides and DR complexes. Therefore, some mutated Ras- and p53-derived peptides could be tumor-specific antigens recognized by CD4+ T cells in an HLA-DR allele-specific manner.