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© Research
Publication : Journal of immunology (Baltimore, Md. : 1950)

Dendritic cells use endocytic pathway for cross-priming class Ib MHC-restricted CD8alphaalpha+TCRalphabeta+ T cells with regulatory properties

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of immunology (Baltimore, Md. : 1950) - 01 Jun 2009

Smith TR, Tang X, Maricic I, Garcia Z, Fanchiang S, Kumar V

Link to Pubmed [PMID] – 19454693

J. Immunol. 2009 Jun;182(11):6959-68

Understanding the mechanisms leading to effective priming of lymphocytes with regulatory properties is crucial for the manipulation of immune responses. CD8alphaalpha(+)TCRalphabeta(+) T cells are a special subset of innate-like lymphocytes that have been shown to be involved in immune regulation. These cells can recognize self-peptides in the context of a class Ib molecule, Qa-1. How self-Ags are processed in the Qa-1 pathway and presented to CD8alphaalpha(+)TCRalphabeta(+) T cells is not understood. In this study we demonstrate a cross-presentation pathway by which bone marrow-derived dendritic cells (DCs) capture apoptotic CD4(+) T cells and process and present TCR-derived peptides in the context of Qa-1 to prime CD8alphaalpha(+)TCRalphabeta(+) T cells. The priming ability of the DCs is enhanced following TLR signaling using TLR3, TLR4, and TLR9 agonists. DC-mediated cross-presentation is inhibited in the presence of endosomal and proteasomal Ag-processing antagonists. Importantly, DCs loaded with apoptotic T cells prime CD8alphaalpha(+)TCRalphabeta(+) T cells in vivo, which in turn provides protection from CD4(+) T cell-mediated autoimmune disease. These data provide a key insight related to processing and presentation of self-Ags in the Qa-1 pathway for priming of CD8alphaalpha(+)TCRalphabeta(+) T cells and have implications for a DC-based immunotherapeutic approach to inflammatory diseases.

https://www.ncbi.nlm.nih.gov/pubmed/19454693