Human CD8+ T cell responses to EBV EBNA1: HLA class I presentation of the (Gly-Ala)-containing protein requires exogenous processing.
Epstein-Barr virus (EBV)-induced cytotoxic T lymphocyte (CTL) responses have been detected against many EBV antigens but not the nuclear antigen EBNA1; this has been attributed to the presence of a glycine-alanine repeat (GAr) domain in the protein. Here we describe the isolation of human CD8+ CTL clones recognizing EBNA1-specific peptides in the context of HLA-B35.01 and HLA-A2.03. Using these clones, we show that full-length EBNA1 is not presented when expressed endogenously in target cells, whereas the GAr-deleted form is presented efficiently. However, when supplied as an exogenous antigen, the full-length protein can be presented on HLA class I molecules by a TAP-independent pathway; this may explain how EBNA1-specific CTLs are primed in vivo.
Blake
N
N
CRC Institute for Cancer Studies, University of Birmingham, United Kingdom.
Lee
S
S
Redchenko
I
I
Thomas
W
W
Steven
N
N
Leese
A
A
Steigerwald-Mullen
P
P
Kurilla
M G
MG
Frappier
L
L
Rickinson
A
A
D000409:Alanine / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology*; D002999:Clone Cells; D018900:Dinucleotide Repeats / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005998:Glycine / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015234:HLA-A Antigens; D000409:Alanine; D005998:Glycine