Stuber, G. and Leder, G. H. and Storkus, W. T. and Lotze, M. T. and Modrow, Susanne and Székely, L. and Wolf, Hans J. and Klein, E. and Kärre, K. and Klein, G.
Identification of wild-type and mutant p53 peptides binding to HLA-A2 assessed by a peptide loading-deficient cell line assay and a novel major histocompatibility complex class I peptide binding assay.
European journal of immunology 24 (3), pp. 765-768.
Mutations of the p53 gene are the most frequently observed genetic changes in human cancers; often leading to an overexpression of the wild-type (wt) p53 protein. Demonstrable T cell reactivity against tumor cells overexpressing wt or mutant p53-derived peptides could support the application of such epitopes in cancer immunotherapies. As the binding of peptide to MHC class I molecules is a prerequisite for antigen-specific T cell recognition, we evaluated the ability of wt and mutant p53 peptides to bind to HLA-A2.1 using two independent flow cytometry-based assay systems, the T2 major histocompatibility complex (MHC) class I peptide stabilization assay (stabilization assay) and the peptide-induced MHC class I reconstitution assay (reconstitution assay). The twenty selected wt sequences each conformed to the previously reported HLA-A2.1 peptide binding motif. Seven of the wt p53 and 2/13 mutant p53 peptides derived from the previously chosen wt peptides bound to HLA-A2.1 in both the stabilization and the reconstitution assays. An additional six wt and six mutant p53 peptides, presumably exhibiting lower affinity for HLA-A2.1, were identified only in the reconstitution assay. Those p53 peptides binding HLA-A2.1 may provide useful immunogens for the generation of HLA-A2.1-restricted cytolytic T lymphocytes in vitro and in vivo.
|Institutions:|| Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene|
|Amino Acid Sequence||MESH|
|Molecular Sequence Data||MESH|
|Tumor Suppressor Protein p53/immunology||MESH|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||06 Apr 2011 07:44|
|Last Modified:||21 Jul 2011 02:10|