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.

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.

• Authors: H Bryden, J MacKenzie, L Andrew, F E Alexander, B Angus, A S Krajewski, A A Armstrong, D Gray, R A Cartwright, E Kane, D H Wright, P Taylor, R F Jarrett
• Journal: International journal of cancer (Int J Cancer) Vol. 72 Issue 4 Pg. 614-8 (Aug 07 1997) ISSN: 0020-7136 [Print] United States
• PMID: 9259400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Antigens, Viral
• EBV-associated membrane antigen, Epstein-Barr virus
• HLA-A Antigens
• Immunodominant Epitopes
• Oncogene Proteins, Viral
• Viral Matrix Proteins

Topics

• Adolescent
• Adult
• Alleles
• Antigens, Neoplasm (genetics, immunology)
• Antigens, Viral (genetics, immunology)
• HLA-A Antigens (genetics, immunology)
• Herpesviridae Infections (genetics, immunology)
• Herpesvirus 4, Human (genetics, immunology)
• Hodgkin Disease (genetics, immunology, virology)
• Humans
• Immunodominant Epitopes (analysis, genetics)
• Mutation
• Oncogene Proteins, Viral (genetics, immunology)
• Tumor Virus Infections (genetics, immunology)
• Viral Matrix Proteins (genetics, immunology)