) The recent association of KS and a subset of AIDS-related lymphomas with the novel gamma-herpesvirus, human herpesvirus-8 (HHV-8), provides the basis for evaluating immunologic responses to this virus, potential immune based mechanisms for tumor development and the design of immunologic strategies for tumor control. To this end, the applicant has established a collaborative group which brings together investigators in AIDS-related malignancies and anti-viral immunology with particular expertise in CTL epitope prediction, T cell vaccination, dendritic cell biology and hematopoietic cell manipulation in HIV disease. Using established techniques, a detailed characterization of the cellular immune response to HHV-8 will be performed. Specifically, the applicant proposes to: 1) identify potential cytotoxic T lymphocyte (CTL) epitopes in coding regions of the HHV-8 genome and test binding of encoded peptides to specific HLA alleleic proteins, 2) determine if predicted peptide epitopes are capable of eliciting a memory CTL response from PBMC of patients with and without KS and whether KS lesions are infiltrated with CTLs specific for predicted HHV-8 epitopes, and 3) evaluate the capacity for ex vivo generated dendritic cells from HIV infected individuals and uninfected controls to serve as antigen presenting cells and elicit a primary CTL response to predicted CTL epitopes of HHV-8. These studies are designed to provide the basis for vaccination or antigen pulsed autologous dendritic cell therapies for AIDS-associated Kaposi's sarcoma or HHV-8-associated AIDS body cavity lymphoma and may provide strategies for preventing these complications of HIV disease.
| Woodberry, Tonia; Suscovich, Todd J; Henry, Leah M et al. (2005) Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins. J Infect Dis 192:622-9 |
| Suscovich, Todd J; Paulose-Murphy, Mini; Harlow, Jason D et al. (2004) Defective immune function of primary effusion lymphoma cells is associated with distinct KSHV gene expression profiles. Leuk Lymphoma 45:1223-38 |
| Brander, C; O'Connor, P; Suscovich, T et al. (2001) Definition of an optimal cytotoxic T lymphocyte epitope in the latently expressed Kaposi's sarcoma-associated herpesvirus kaposin protein. J Infect Dis 184:119-26 |
| Brander, C; Suscovich, T; Lee, Y et al. (2000) Impaired CTL recognition of cells latently infected with Kaposi's sarcoma-associated herpes virus. J Immunol 165:2077-83 |
| Jones, D; Ballestas, M E; Kaye, K M et al. (1998) Primary-effusion lymphoma and Kaposi's sarcoma in a cardiac-transplant recipient. N Engl J Med 339:444-9 |
