Evidence for the presentation of major histocompatibility complex class I-restricted Epstein-Barr virus nuclear antigen 1 peptides to CD8+ T lymphocytes.
The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) is expressed in all EBV-associated tumors, making it an important target for immunotherapy. However, evidence for major histocompatibility complex (MHC) class I-restricted EBNA1 peptides endogenously presented by EBV-transformed B and tumor cells remains elusive. Here we describe for the first time the identification of an endogenously processed human histocompatibility leukocyte antigen (HLA)-B8-restricted EBNA1 peptide that is recognized by CD8+ T cells. T cell recognition could be inhibited by the treatment of target cells with proteasome inhibitors that block the MHC class I antigen processing pathway, but not by an inhibitor (chloroquine) of MHC class II antigen processing. We also demonstrate that new protein synthesis is required for the generation of the HLA-B8 epitope for T cell recognition, suggesting that defective ribosomal products (DRiPs) are the major source of T cell epitopes. Experiments with protease inhibitors indicate that some serine proteases may participate in the degradation of EBNA1 DRiPs before they are further processed by proteasomes. These findings not only provide the first evidence of the presentation of an MHC class I-restricted EBNA1 epitope to CD8+ T cells, but also offer new insight into the molecular mechanisms involved in the processing and presentation of EBNA1.
Voo
Kui Shin
KS
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Fu
Tihui
T
Wang
Helen Y
HY
Tellam
Judy
J
Heslop
Helen E
HE
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
Wang
Rong-Fu
RF
D000595:Amino Acid Sequence; D000937:Antigen-Antibody Reactions; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology
D019309:Epstein-Barr Virus Nuclear Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; C417029:EBV-encoded nuclear antigen 1