Lytic and Latent Antigens of the Human Gammaherpesviruses Kaposi's Sarcoma-Associated Herpesvirus and Epstein-Barr Virus Induce T-Cell Responses with Similar Functional Properties and Memory Phenotypes

Abstract

The cellular immunity against Kaposi's sarcoma-associated herpesvirus (KSHV) is poorly characterized and has not been compared to T-cell responses against other human herpesviruses. Here, novel and dominant targets of KSHV-specific cellular immunity are identified and compared to T cells specific for lytic and latent antigens in a second human gammaherpesvirus, Epstein-Barr virus. The data identify a novel HLA-B57-and HLA-B58-restricted epitope in the Orf57 protein and show consistently close parallels in immune phenotypes and functional response patterns between cells targeting lytic or latent KSHV-and EBV-encoded antigens, suggesting common mechanisms in the induction of these responses.

Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral IRF3 Modulates Major Histocompatibility Complex Class II (MHC-II) Antigen Presentation through MHC-II Transactivator-Dependent and -Independent Mechanisms: Implications for Oncogenesis

“…T-cell responses to KSHV-encoded latent antigens and lytic antigens have been identified in both healthy immunocompetent donors and immunocompromised patients (32)(33)(34)(35)(36)(37). Although generally weak, KSHV-specific CD8 T cells responses are more frequent, diverse, and strong in asymptomatic KSHV-infected patients than Kaposi's sarcoma patients (38).…”

T-cell immunity to Kaposi sarcoma–associated herpesvirus: recognition of primary effusion lymphoma by LANA-specific CD4+ T cells

“…33,34 These KSHV-specific responses were also lower than those reported in similar studies using individuals co-infected with HIV on HAART therapy, yet they showed a similar immunodominance profile with epitopes from LANA more frequently recognized than Kaposin. 9,10 These responses did seem more frequent than those described in HIVinfected donors with KS before HAART 2 or in transplant patients with KS before changing their immunosuppressive regime. 35 Because the ex vivo T-cell responses were weak, we generated T-cell clones for further study.…”

“…36 However, our findings show some contrast to what may be expected based on studies of ex vivo stimulation of donors' PBMCs with overlapping LANA peptides that resulted in stimulation of mostly CD8 ϩ T cells. 9 Furthermore, ex vivo stimulation of PBMCs with dendritic cells sensitized with overlapping LANA peptides has been shown to stimulate CD8 ϩ T-cell responses. 5 Using these LANA-specific CD4 ϩ clones to probe recognition of LANA-expressing cells, we found that EBV-transformed B cells, cells that have an intact class II antigen processing pathway, could efficiently process and present LANA antigens.…”

“…Thus, HIV-infected patients on HAART who control KSHV have been found to make T-cell responses to LANA, MCD patients make responses comparable to HIV patients on HAART, but patients with KS disease have very weak or no detectable responses. [7][8][9][10][11] The administration of HAART to HIVassociated KS patients has been associated with the detection and increase in KSHV-specific responses over time. 2,12 Little is known, however, about the size of responses made to the potential tumor antigens vFLIP or vCyclin in healthy donors or patients with disease.…”

Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence?

“…CD4 + T-lymphocytes are also important in controlling KSHV infection, but CD8 + T-lymphocyte epitopes are most frequently found in sera from HIV/KSHV-infected patients (Bihl et al, 2007;Brander et al, 2001;Robey et al, 2010).…”