Endogenous presentation of CD8+ T cell epitopes from Epstein-Barr virus-encoded nuclear antigen 1.
Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type-dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I-restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8+ T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8+ T cell epitopes from EBNA1.
Tellam
Judy
J
EBV Unit, Tumour Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, 300 Herston Road, Brisbane (Qld) 4006, Australia.
Connolly
Geoff
G
Green
Katherine J
KJ
Miles
John J
JJ
Moss
Denis J
DJ
Burrows
Scott R
SR
Khanna
Rajiv
R
D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D011994:Recombinant Proteins; D003513:Cycloheximide; C417029:EBV-encoded nuclear antigen 1