title: T-cell immunity to Kaposi sarcoma-associated herpesvirus: recognition of primary effusion lymphoma by LANA-specific CD4+ T cells.
abstract: T-cell immunity is important for controlling Kaposi sarcoma-associated herpesvirus (KSHV) diseases such as the endothelial cell malignancy Kaposi sarcoma, or the B-cell malignancy, primary effusion lymphoma (PEL). However, little is known about KSHV-specific T-cell immunity in healthy donors and immune control of disease. Using PBMCs from healthy KSHV-infected donors, we found weak ex vivo responses to the KSHV latent antigens LANA, vFLIP, vCyclin, and Kaposin, with LANA most frequently recognized. CD4(+) T-cell clones specific to LANA, a protein expressed in all KSHV-infected cells and malignancies, were established to determine whether they could recognize LANA-expressing cells. B-cell targets expressing or fed LANA protein were consistently recognized by the clones; however, most PEL cell lines were not. PELs express the KSHV protein vIRF3 that inhibits promoter function of the HLA class II transactivator, decreasing expression of genes controlled by this transactivator. Re-expressing the class II transactivator in the PELs increased expression of downstream targets such as HLA class II and restored recognition but not killing by the LANA-specific clones. We suggest that PELs are poorly controlled in vivo because of inefficient recognition and killing by T cells.
authors.affiliation: School of Cancer Sciences and Medical Research Council Centre for Immune Regulation, The University of Birmingham, Birmingham, United Kingdom.
authors.forename: Shereen
authors.initials: S
authors.lastname: Sabbah
authors.forename: Ya Jankey
authors.initials: YJ
authors.lastname: Jagne
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zuo
authors.forename: Thushan
authors.initials: T
authors.lastname: de Silva
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Ahasan
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Sarah
authors.initials: S
authors.lastname: Rowland-Jones
authors.forename: Katie L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hislop
mesh_terms: D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D054685:Lymphoma, Primary Effusion / Q000276:immunology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000276:immunology; D014019:Tissue Donors; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; C109540:latency-associated nuclear antigen