CD4+ T Cells from Peripheral Blood of a Melanoma Patient Recognize Peptides Derived from Nonmutated Tyrosinase
Abstract
Tyrosinase is an antigen that is expressed by normal melanocytes as well as melanoma cells, against which responses by autologous T cells have been detected. Although CD4 + T cells play an important role in tumor immunity in animal tumor models, little information about CD4 + T-cell immunity against human tumors exists. Here, we report that CD4 + T cells from the peripheral blood of a patient with melanoma respond to synthetic peptides derived from nonmutated tyrosinase. T-cell clones were generated that recognized the tyrosinase p386–406 peptide when it was presented by the HLA-DR15 ( DRB1*1501 ) molecule. The CD4 + T-cell clone also recognized autologous EBV-transformed B-lymphoblastoid cell lines that had been pulsed with the lysate of melanoma cells. The synthetic tyrosinase p386–406 peptide was capable of binding to HLA-DR15 ( DRB1*1501 ) molecules on cell surface of DR15 homozygous cells. Thus, the finding that nonmutated tyrosinase peptides are immunogenic in a melanoma patient may provide the basis for the development of cancer immunotherapy, based on knowledge of synthetic tumor-associated peptide antigens. 1 To whom requests for reprints should be addressed, at Department of Pathology, Asahikawa Medical College, Nishikagura 4-5-3-11, Asahikawa, 078, Japan.