An N-glycosylated tyrosinase epitope associates with newly synthesized MHC class I molecules in melanoma cells.
Endogenous antigenic epitopes are presented to CD8+ T cells by MHC class I molecules. Many endogenous antigens are glycoproteins, and it is not clear what effect the attachment of carbohydrate to potential immunogenic epitopes has on their processing and presentation (i.e., is the carbohydrate moiety removed prior to presentation, or is it presented along with the peptide to T cells?). A major question in this regard is whether natural antigenic epitopes that possess N-linked carbohydrate can associate with class I molecules during assembly in the endoplasmic reticulum (ER). One such antigenic epitope, corresponding to amino acids 369-377 of the enzyme tyrosinase, possesses an N-linked glycosylation site. We have studied the transport and loading of this epitope in streptolysin O-permeabilized melanoma cells. We show here that that the glycosylated epitope is capable of loading onto newly synthesized HLA-A2 molecules in the ER of two melanoma cell lines. The results are discussed in respect to the processing and presentation of the tyrosinase epitope.
Androlewicz
M J
MJ
Immunology Program, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. androlma@moffitt.usf.edu
D001692:Biological Transport / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D006031:Glycosylation; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000201:enzymology* / Q000276:immunology*; D014442:Monophenol Monooxygenase / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000276:immunology; D014407:Tumor Cells, Cultured
D000939:Epitopes; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D014442:Monophenol Monooxygenase