TAP-independent self-peptides enhance T cell recognition of immune-escaped tumors

The Journal of Clinical Investigation
Elien M DoorduijnThorbald van Hall

Abstract

Tumor cells frequently escape from CD8+ T cell recognition by abrogating MHC-I antigen presentation. Deficiency in processing components, like the transporter associated with antigen processing (TAP), results in strongly decreased surface display of peptide/MHC-I complexes. We previously identified a class of hidden self-antigens known as T cell epitopes associated with impaired peptide processing (TEIPP), which emerge on tumor cells with such processing defects. In the present study, we analyzed thymus selection and peripheral behavior of T cells with specificity for the prototypic TEIPP antigen, the "self" TRH4 peptide/Db complex. TEIPP T cells were efficiently selected in the thymus, egressed with a naive phenotype, and could be exploited for immunotherapy against immune-escaped, TAP-deficient tumor cells expressing low levels of MHC-I (MHC-Ilo). In contrast, overt thymus deletion and functionally impaired TEIPP T cells were observed in mice deficient for TAP1 due to TEIPP antigen presentation on all body cells in these mice. Our results strongly support the concept that TEIPPs derive from ubiquitous, nonmutated self-antigens and constitute a class of immunogenic neoantigens that are unmasked during tumor immune evasion. The...Continue Reading

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Citations

Jan 23, 2016·Current Opinion in Immunology·Federico GarridoThorbald van Hall
Jan 20, 2016·The Journal of Clinical Investigation·Rolf Kiessling
Mar 7, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ida HafstrandAdnane Achour
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Aug 23, 2018·The Journal of Experimental Medicine·Mathieu Gigoux, Jedd Wolchok
Jul 7, 2019·Nature Reviews. Cancer·Christof C SmithJonathan S Serody
Aug 23, 2019·Nature Communications·Greta GarridoEli Gilboa
Aug 18, 2018·The Journal of Experimental Medicine·Koen A MarijtThorbald van Hall
Feb 6, 2020·Médecine sciences : M/S·Adrien Vouilloz, Laurent Serre
Dec 1, 2018·ELife·Ron S GejmanDavid A Scheinberg
Apr 16, 2020·Cancers·Marit J van ElsasSjoerd H van der Burg
Jun 24, 2017·Cancer Immunology Research·Elien M DoorduijnThorbald van Hall
Apr 17, 2020·Cancer Immunology Research·Greta GarridoEli Gilboa
Jun 4, 2021·Molecular Immunology·M L M JongsmaR M Spaapen
Jul 3, 2021·International Journal of Molecular Sciences·Elena Shklovskaya, Helen Rizos
Jun 20, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sarah ShigdarVittorio de Franciscis
Jul 31, 2019·Journal of Proteome Research·Elena LorenteDaniel López

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Methods Mentioned

BETA
transgenic
flow cytometry
FCS
reverse transcription PCR
PCR
FACS
flow
ELISA

Software Mentioned

GraphPad Prism

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