Analysis of major histocompatibility complex class I, TAP expression, and LMP2 epitope sequence in Epstein-Barr virus-positive Hodgkin's disease

• Published in: Blood Vol. 92; no. 7; pp. 2477 - 2483
• Main Authors: MURRAY, P. G, CONSTANDINOU, C. M, CROCKER, J, YOUNG, L. S, AMBINDER, R. F
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 01.10.1998
• Subjects: Alleles; Antigen Presentation; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B, Member 3; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Base Sequence; Biological and medical sciences; Epitopes - immunology; European Continental Ancestry Group - genetics; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Herpesviridae Infections - genetics; Herpesviridae Infections - metabolism; Herpesviridae Infections - virology; Herpesvirus 4, Human - isolation & purification; HLA Antigens - biosynthesis; HLA Antigens - genetics; HLA-A2 Antigen - genetics; HLA-A2 Antigen - immunology; Hodgkin Disease - genetics; Hodgkin Disease - immunology; Hodgkin Disease - metabolism; Hodgkin Disease - virology; Humans; Immunologic Surveillance; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; T-Lymphocytes, Cytotoxic - immunology; Tumor Virus Infections - genetics; Tumor Virus Infections - metabolism; Tumor Virus Infections - virology; Viral Matrix Proteins - biosynthesis; Viral Matrix Proteins - genetics; Gammaherpesvirinae; Human; HLA-System; Membrane protein; Antigenic determinant; Herpesviridae; Major histocompatibility system; Hodgkin disease; Malignant hemopathy; Epstein Barr virus; Lymphoma; Infection; Virus; Latent; HLA-A-Locus; Histocompatibility restriction; Lymphoproliferative syndrome; Viral disease; Class I histocompatibility antigen; Carrier protein
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v92.7.2477

The Epstein-Barr virus (EBV)-encoded latent membrane proteins, LMP1 and LMP2, are consistently expressed by the malignant Hodgkin/Reed-Sternberg (HRS) cells of EBV-associated Hodgkin's disease (HD). Cytotoxic T lymphocyte (CTL) responses to both of these proteins have been shown in the blood of EBV-seropositive individuals, yet in HD the apparent failure of the CTL response to eliminate HRS cells expressing LMP1 and LMP2 in vivo has given rise to the suggestion that HD may be characterized by the presence of defects in antigen processing/presentation or in CTL function. This study has used immunohistochemistry to show high-level expression of major histocompatibility complex (MHC) class I molecules by the HRS cells of EBV-associated HD and either low level or absence of expression of MHC class I molecules on HRS cells of EBV-negative tumors. In addition, HRS cells expressed high levels of transporter-associated proteins (TAP-1, -2), irrespective of the presence of latent EBV infection. These results suggest that global downregulation of MHC class I molecules does not account for the apparent ability of EBV-infected HRS cells to evade CTL responses, but may be important in the understanding of EBV-negative disease. We have also sequenced an epitope in LMP2A (CLGGLLTMV) that is restricted through HLA A2.1, a relatively common allele in Caucasian populations, and showed that this epitope is wild type in a small group of EBV-associated HLA A2.1-positive HD tumors. This result may be relevant to proposed immunotherapeutic approaches for EBV-positive HD patients that target CTL epitopes.