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Determination of HLA-A02 antigen status in Hodgkin's disease and analysis of an HLA-A02-restricted epitope of the Epstein-Barr virus LMP-2 protein.

Abstract：

: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.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Bryden H,MacKenzie J,Andrew L,Alexander FE,Angus B,Krajewski AS,Armstrong AA,Gray D,Cartwright RA,Kane E,Wright DH,Taylor P,Jarrett RF

doi

10.1002/(sici)1097-0215(19970807)72:4<614::aid-ijc

subject

Has Abstract

pub_date

1997-08-07 00:00:00

pages

614-8

issue

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19970807)72:4<614::AID-IJC

journal_volume

pub_type

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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.

Determination of HLA-A02 antigen status in Hodgkin's disease and analysis of an HLA-A02-restricted epitope of the Epstein-Barr virus LMP-2 protein.