Expression Hierarchy of T Cell Epitopes from Melanoma Differentiation Antigens: Unexpected High Level Presentation of Tyrosinase-HLA-A2 Complexes Revealed by Peptide-Specific, MHC-Restricted, TCR-Like Antibodies

作者: Yael Michaeli , Galit Denkberg , Keren Sinik , Liz Lantzy , Chiang Chih-Sheng

DOI: 10.4049/JIMMUNOL.0801898

关键词: CD8T-cell receptorImmunotherapyBiologyImmunologyCellMajor histocompatibility complexCell biologyMelanomaImmune systemAntibody

摘要: Peptide Ags presented by class I MHC molecules on human melanomas and that are recognized CD8 + T cells the subjects of many studies antitumor immunity represent attractive candidates for therapeutic approaches. However, no direct quantitative measurements exist to reveal their expression hierarchy cell surface. Using novel recombinant Abs which bind these with a peptide-specific, MHC-restricted manner, we demonstrate defined pattern peptide-HLA-A2 complexes derived from three major differentiation Ags: gp100, Melan-A/Mart-1, tyrosinase. Studying melanoma lines multiple patients, surprisingly high level presentation tyrosinase-derived moderate very low other Ags. No correlation between Ag mRNA was found; however, protein stability may play role. These results provide new insights into characteristics particularly important when such targets being considered immunotherapy. shed light relationships immune response cancer

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