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Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+ and CD4+ T cells.

ABSTRACT: To better understand the mechanisms of intracellular trafficking and presentation of exogenous peptides by antigen-presenting cells (APC), we compared the handling of overlapping 24-mer peptides from HIV Nef either mixed or covalently linked in tandem in one protein. Once internalized, peptides trafficked not only to endosomes but also to cytosol, and activated CD8(+) and CD4(+) T cells. In contrast, whole protein was found to traffic only to the endosomal compartments, and primarily activated CD4(+) T cells. Finally, with adjuvant, overlapping peptides were capable of protecting against lethal viral challenge, whereas the intact protein was less protective. These data suggest that overlapping long peptides are cross-presented through more varied intracellular routes and are more efficient in priming protective immunity than the whole protein.

SUBMITTER: Zhang H

PROVIDER: S-EPMC2666570 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+ and CD4+ T cells.

Zhang Hongwei H Hong Hai H Li Demin D Ma Shiwu S Di Ying Y Stoten Adam A Haig Neil N Di Gleria Katalin K Yu Zhanru Z Xu Xiao-Ning XN McMichael Andrew A Jiang Shisong S

The Journal of biological chemistry 20090204 14

To better understand the mechanisms of intracellular trafficking and presentation of exogenous peptides by antigen-presenting cells (APC), we compared the handling of overlapping 24-mer peptides from HIV Nef either mixed or covalently linked in tandem in one protein. Once internalized, peptides trafficked not only to endosomes but also to cytosol, and activated CD8(+) and CD4(+) T cells. In contrast, whole protein was found to traffic only to the endosomal compartments, and primarily activated C ...[more]

PMID: 19193636

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Project description:Purpose:Injection of an antigen into the anterior chamber of the eye induces a peripheral antigen-specific immune modulation mechanism, known as anterior chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity experiments argue that the subretinal space (SR) of the eye displays properties similar to ACAID. However, no investigation was performed regarding the differential impact of a subretinal antigen injection on peripheral CD4+ versus CD8+ T cells, on the potential immune deviation regarding Th profiles, and on the antigen-specificity of the inhibition. A better understanding of these mechanisms is crucial to improve safety and immunomonitoring of ongoing therapeutic approaches targeting the SR. The aim of this study is to characterize the proliferative capacities and cytokine patterns of antigen-specific CD4+ and CD8+ T cells after a subretinal injection of antigen in mice. Methods:Ubiquitously Transcribed tetratricopeptide repeat gene Y-linked (UTY) and DEAD Box polypeptide 3 Y-linked (DBY) peptides which respectively include MHCI- and MHCII-restricted T-cell epitopes of the mouse HY male antigen, were injected into the subretinal space of C57BL/6 female mice. 2?weeks later, these mice were immunized subcutaneously with these peptides and compared to control mice. A week later, T-cell immune responses were analyzed by IFN? ELISpot assays and cytokine measurements (IL-2, IL-4, IL-6, IL-10, IL-13, IL-17a, IFN?, TNF?, GM-CSF, and MCP-1) in the spleen and with proliferation assays in draining lymph nodes. Results:Immune cells from mice that received HY peptides in the SR before immunization, compared with those from control immunized mice, secreted significantly smaller quantities of Th1/Tc1, Th2/Tc2, and Th17/Tc17 cytokines, and HY-specific CD4+ T cells proliferated less in response to HY peptides. Conclusion:Taken together, our data clearly demonstrate that the subretinal injection of HY peptides induces a systemic HY-specific inhibition of conventional Th profiles and CD8+ T cells. We propose to call this phenomenon SRAII, for subretinal-associated immune inhibition.

Dataset Information

Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+ and CD4+ T cells.

Publications

Comparing pooled peptides with intact protein for accessing cross-presentation pathways for protective CD8+ and CD4+ T cells.

Similar Datasets

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