Cutting Edge: Prolonged Antigen Presentation after Herpes Simplex Virus-1 Skin Infection

Abstract

It has been reported that MHC class I-restricted Ag presentation persists for only a short period following infection with certain pathogens, declining in parallel with the emergence of specific CTL activity. We have examined this issue in the case of murine infection with HSV-1. We found that the period of Ag presentation capable of priming naive CD8+ T cells is comparatively prolonged, persisting for at least 7 days after infection, and continuing despite the appearance of localized CTL activity. Ag presentation was abbreviated to 3 or 4 days postinfection by surgical excision of the inoculation site early after infection. This intervention attenuated the size of the primary CTL response, implying that prolonged presentation is necessary to drive maximal CTL expansion. Combined, these data show that, in some types of infection, CTL priming can extend well beyond the first 24–48 h after primary inoculation.

Immunization with Lentiviral Vector-Transduced Dendritic Cells Induces Strong and Long-Lasting T Cell Responses and Therapeutic Immunity

“…It is possible that Ag ligand persistence sufficient to drive or help previously stimulated T cells may be important to support the long-lasting effector responses we observe, but insufficient to drive induction of the naive OT-1 T cells used in the assay. Other recent studies have shown that for maximal CTL induction, a short period of stimulation (24 h), not prolonged Ag presentation, is required (52,64). These studies suggest that the magnitude and duration of CD8 T cell responses are determined by the initial clonal burst of T cell activation resulting from an initial period of engagement with APCs.…”

“…The in vivo Ag presentation assay was performed as previously described (52). Briefly, mice were injected in the footpad with 500,000 DCs that were transduced with lvv expressing OVA or pulsed with SIINFEKL peptide or OVA protein as indicated.…”

“…At the indicated time points, 5 million OT-I cells labeled with CFSE were administered through the tail vein. Forty-eight hours after injection of OT-I cells, draining popliteal LN and contralateral LN cells were collected and stained with anti-V␣2 and anti-V␤ 5.1-5.2 and analyzed for proliferation as described previously (52).…”

Sculpting the immunological response to dengue fever by polytopic vaccination

“…This process leads to 0.5% diversity of the memory repertoire, because 0.58 10 ≈ 0.5%. In vivo T cell tracking experiments have shown that T cells continue to interact with antigen in the lymph node up to 5 days after initial stimulation [41,42], and examinations of draining lymph nodes have found that antigen capable of priming naive T cells is present up to 7 days post inoculation [43], both of which support the concept that the selection process may continue during each T cell division. Although the exact mechanism of the T cell expansion during the primary immune response remains elusive, it is observed that the expansion of the T cells is nonlinear [44], and that in most cases there is competition among the T cells for the presented antigen [45,46].…”

Recombinant lentivector as a genetic immunization vehicle for antitumor immunity

“…It has been suggested that extended interaction between APCs and T cells is required to elicit fit T cells that can respond to homeostasis cytokines for survival [70][71][72] . In addition, prolonged Ag presentation might be required to have sufficient time for all possible cognate T cells to be screened by Ag presenting APCs and induce maximal CTL responses 73 . Furthermore, it has recently been demonstrated that Ag presentation in the late stage of viral infection may be needed to generate memory CD4 and CD8 T cell responses [74][75][76] .…”