Determination of HLA-A*02 antigen status in Hodgkin's disease and analysis of an HLA-A*02-restricted epitope of the Epstein-Barr virus LMP-2 protein.
There is good evidence for an association between Epstein-Barr virus (EBV) and Hodgkin's disease (HD). In approximately one-third of cases, the EBV genome is detectable in Reed-Sternberg (RS) cells and there is expression of the viral nuclear antigen EBNA-1 and the latent membrane protein LMP-1. Expression of LMP-2 has been demonstrated at the mRNA level, and it is presumed that the protein is expressed alongside LMP-1. The LMP-2 protein is known to contain an epitope presented to cytotoxic T-cells which is restricted through the HLA class I antigen A*0201 in healthy seropositive individuals. Since most HLA-A*02-positive Caucasians are HLA-A*0201-positive, it was hypothesized that HLA-A*02-positive individuals would be under-represented among Caucasians with EBV-associated HD. HLA-A*02 status was determined, using flow cytometry and/or the polymerase chain reaction, for 276 individuals including 176 cases of HD. There was no significant difference between the frequency of HLA-A*02 positivity in HD cases and controls, and between EBV-associated and non-associated cases of HD. The A*02 alleles of 14 cases of EBV-associated HD were further subtyped using nested PCR; all except one case were found to be A*0201-positive. We therefore investigated whether there was any evidence for mutation of the epitope representing amino acids 426-434 of LMP-2a which is restricted through HLA-A*0201. In 10/11 cases the nucleotide sequence encoding this epitope was identical to the published sequence; in the remaining case there was a mutation which would not be expected to alter the conformation of the epitope. Overall, our data suggest that other mechanisms of immune escape must be operative in EBV-associated HD.
Bryden
H
H
Department of Veterinary Pathology, Veterinary School, University of Glasgow, UK.
MacKenzie
J
J
Andrew
L
L
Alexander
F E
FE
Angus
B
B
Krajewski
A S
AS
Armstrong
A A
AA
Gray
D
D
Cartwright
R A
RA
Kane
E
E
Wright
D H
DH
Taylor
P
P
Jarrett
R F
RF
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis* / Q000235:genetics; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015234:HLA-A Antigens; D016056:Immunodominant Epitopes; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins