Tumors with processing defects display novel tumor antigens via the non-classical HLA-E

Abstract

Event Abstract Back to Event Tumors with processing defects display novel tumor antigens via the non-classical HLA-E Elien M. Doorduijn1, Claudia Cunha Oliveira1, Bianca Querido1, Marjolein Sluijter1 and Thorbald Van Hall1* 1 Leiden University Medical Center, Netherlands The non-classical HLA-E accommodates monomorphic leader peptides and functions as a ligand for germ line receptors CD94/NKG2, expressed by natural killer cells and CD8+ T cells. We previously described that the conserved peptides are replaced by a novel peptide repertoire of surprising diversity as a result of impairments in the antigen processing pathway. Whereas the monomorphic peptide/HLA-E complex represents the ‘innate face’ of HLA-E, this novel peptide repertoire constitutes immunogenic neo-antigens for CD8+ T cells. We found that T cells restricted by the mouse equivalent Qa-1b dominantly participated in the response to tumors with processing deficiencies. A surprisingly wide spectrum of target cells, irrespective of transformation status, MHC background or type of processing deficiency was recognized by this T cell subset, complying with the conserved nature of Qa-1b. Target cell recognition depended on T cell receptor and Qa-1b interaction and immunization with identified peptide-epitopes demonstrated in vivo priming of CD8+ T cells. Current investigations are focused on the involved rearranged TCRs that confer the tumor reactivity Although this CD8 T cell subset does arise in the periphery of TCR-transgenic animals, the thymic selection process seems to be very inefficient. Our data reveal that HLA-E and its mouse homolog Qa-1b are important for the defense against processing deficient cells by displacing the monomorphic leader peptides, which relieves the inhibition through CD94/NKG2A on lymphocytes and by presenting a novel repertoire of immunogenic peptides, which recruits a subset of cytotoxic CD8+ T cells. References Oliveira CC, van Veelen PA, Querido B, de Ru A, Sluijter M, Laban S, Drijfhout JW, van der Burg SH, Offringa R, van Hall T. The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen-processing defects. J Exp Med. 2010 Jan 18;207(1):207-21. Seidel UJ, Oliveira CC, Lampen MH, Hall Tv. A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens. Cancer Immunol Immunother. 2012 Jan;61(1):119-25. van Hall T, Wolpert EZ, van Veelen P, Laban S, van der Veer M, Roseboom M, Bres S, Grufman P, de Ru A, Meiring H, de Jong A, Franken K, Teixeira A, Valentijn R, Drijfhout JW, Koning F, Camps M, Ossendorp F, Kärre K, Ljunggren HG, Melief CJ, Offringa R. Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Nat Med. 2006 Apr;12(4):417-24. Lampen MH, van Hall T. Strategies to counteract MHC-I defects in tumors. Curr Opin Immunol. 2011 Apr;23(2):293-8. Oliveira CC, Querido B, Sluijter M, Derbinski J, van der Burg SH, van Hall T. Peptide transporter TAP mediates between competing antigen sources generating distinct surface MHC class I peptide repertoires. Eur J Immunol. 2011 Nov;41(11):3114-24. Keywords: HLA-E, CTL, neoantigen, Qa-1, tumorimmunology Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Doorduijn EM, Cunha Oliveira C, Querido B, Sluijter M and Van Hall T (2013). Tumors with processing defects display novel tumor antigens via the non-classical HLA-E. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00728 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Thorbald Van Hall, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands, t.van_hall@lumc.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Elien M Doorduijn Claudia Cunha Oliveira Bianca Querido Marjolein Sluijter Thorbald Van Hall Google Elien M Doorduijn Claudia Cunha Oliveira Bianca Querido Marjolein Sluijter Thorbald Van Hall Google Scholar Elien M Doorduijn Claudia Cunha Oliveira Bianca Querido Marjolein Sluijter Thorbald Van Hall PubMed Elien M Doorduijn Claudia Cunha Oliveira Bianca Querido Marjolein Sluijter Thorbald Van Hall Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.