Projects per year
T cell immunity is important for controlling Kaposi's sarcoma-associated herpesvirus (KSHV) diseases such as the endothelial cell malignancy Kaposi's 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 if 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 which inhibits promoter function of the HLA class II transactivator CIITA, decreasing expression of genes controlled by this transactivator. Re-expressing CIITA 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 due to inefficient recognition and killing by T cells.
|Number of pages||10|
|Publication status||Published - 10 Jan 2012|
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- 1 Finished
Immunity to Gamma-Herpesviruses
1/04/07 → 30/09/10
Project: Research Councils