Endogenous presentation of CD8+T cell epitopes from Epstein-Barr virus–encoded nuclear antigen 1

Tellam, Judy, Connolly, Geoff, Green, Katherine J., Miles, John J., Moss, Denis J., Burrows, Scott R., and Khanna, Rajiv (2004) Endogenous presentation of CD8+T cell epitopes from Epstein-Barr virus–encoded nuclear antigen 1. The Journal of Experimental Medicine, 199 (10). pp. 1421-1431.

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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.

Item ID: 45618
Item Type: Article (Research - C1)
ISSN: 1540-9538
Keywords: EBNA1, CD8, T cell, antigen processing, DRiPs, proteasome
Funders: National Health and Medical Research Council of Australia (NHMRC)
Date Deposited: 07 Sep 2016 03:11
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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