International Immunology, Vol 9, 1537-1543, Copyright © 1997 by Oxford University Press
R Khanna, SR Burrows, PM Steigerwald-Mullen, DJ Moss, MG Kurilla and L Cooper
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the only viral
protein consistently expressed in all malignancies associated with EBV and
there is now convincing evidence to suggest that EBNA1 is not recognized by
MHC class I-restricted cytotoxic T lymphocytes (CTL). The lack of
recognition of EBNA1 has been attributed to a cis-acting inhibitory effect
of glycine-alanine repetitive (G-Ar) sequences on the endogenous processing
of this antigen through the class I pathway. In the present study we have
explored the possibility of targeting EBNA1 through an alternative
mechanism using the MHC class II pathway. Using purified EBNA1 protein, we
demonstrate here that CD4+ CTL can efficiently recognize EBV-transformed B
cells and Burkitt's lymphoma cells following exogenous sensitization with
this antigen, and this immune recognition is not affected by the G-Ar
domain within EBNA1. Analysis of the processing mechanism revealed that
intracellular loading of class II molecules with an EBNA1 epitope occurs
through an HLA-DM-independent pathway. These results highlight a novel
mechanism for immune recognition of EBNA1 and also demonstrate that the
G-Ar- mediated protection from processing can be overridden if this antigen
is presented through the class II pathway.
ARTICLES
Targeting Epstein-Barr virus nuclear antigen 1 (EBNA1) through the class II pathway restores immune recognition by EBNA1-specific cytotoxic T lymphocytes: evidence for HLA-DM-independent processing
Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
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