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.
Murakami
S
S
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Yokomizo
H
H
Matsushita
S
S
Ogawa
M
M
Nishimura
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D003080:Cold Temperature; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D017354:Point Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology*
D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D010455:Peptides; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)