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Mensali N, Grenov A, Pati NB, et al. Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity. Oncoimmunology. 2019;8(3):1558663doi: 10.1080/2162402X.2018.1558663.
Mensali, N., Grenov, A., Pati, N. B., Dillard, P., Myhre, M. R., Gaudernack, G., Kvalheim, G., Inderberg, E. M., Bakke, O., & Wälchli, S. (2019). Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity. Oncoimmunology, 8(3), 1558663. https://doi.org/10.1080/2162402X.2018.1558663
Mensali, Nadia, et al. "Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity." Oncoimmunology vol. 8,3 (2019): 1558663. doi: https://doi.org/10.1080/2162402X.2018.1558663
Mensali N, Grenov A, Pati NB, Dillard P, Myhre MR, Gaudernack G, Kvalheim G, Inderberg EM, Bakke O, Wälchli S. Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity. Oncoimmunology. 2019 Jan 11;8(3):1558663. doi: 10.1080/2162402X.2018.1558663. eCollection 2019. PMID: 30723591; PMCID: PMC6350688.
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Oncoimmunology. 2019 Jan 11;8(3):1558663. doi: 10.1080/2162402X.2018.1558663. eCollection 2019.

Antigen-delivery through invariant chain (CD74) boosts CD8 and CD4 T cell immunity.

Oncoimmunology

Nadia Mensali, Amalie Grenov, Niladri Bhusan Pati, Pierre Dillard, Marit Renée Myhre, Gustav Gaudernack, Gunnar Kvalheim, Else Marit Inderberg, Oddmund Bakke, Sébastien Wälchli

Affiliations

  1. Department of Cellular Therapy, Department of Oncology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
  2. Department of Molecular Biosciences, University of Oslo, Oslo, Norway.
  3. Centre for Immune Regulation, University of Oslo, Oslo, Norway.
  4. Department of Cancer Immunology, Institute for cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.

PMID: 30723591 PMCID: PMC6350688 DOI: 10.1080/2162402X.2018.1558663

Abstract

Eradication of tumors by the immune system relies on the efficient activation of a T-cell response. For many years, the main focus of cancer immunotherapy has been on cytotoxic CD8 T-cell. However, stimulation of CD4 helper T cells is critical for the promotion and maintenance of immune memory, thus a good vaccine should evoke a two-dimensional T-cell response. The invariant chain (Ii) is required for the MHC class II heterodimer to be correctly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells (APC). We previously showed that by replacing the Ii CLIP peptide by an MHC-I cancer peptide, we could efficiently load MHC-I. This prompted us to test whether longer cancer peptides could be loaded on both MHC classes and whether such peptides could be accommodated in the CLIP region of Ii. We here present data showing that expanding the CLIP replacement size leads to T-cell activation. We demonstrate by using long peptides that APCs can present peptides from the same Ii molecule on both MHC-I and -II. In addition, we present evidence that antigen presentation after Ii-loading was superior to an ER-targeted minigene construct, suggesting that ER-localization was not sufficient to obtain efficient MHC-II loading. Finally, we verified that Ii-expressing dendritic cells could prime CD4

Keywords: T cells; TCR; Vaccines; dendritic cells; invariant chain

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