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Deciphering CD4+ T cell specificity using novel MHC-TCR chimeric receptors.

Abstract：

:αβ T cell antigen receptors (TCRs) bind complexes of peptide and major histocompatibility complex (pMHC) with low affinity, which poses a considerable challenge for the direct identification of αβ T cell cognate peptides. Here we describe a platform for the discovery of MHC class II epitopes based on the screening of engineered reporter cells expressing novel pMHC-TCR (MCR) hybrid molecules carrying cDNA-derived peptides. This technology identifies natural epitopes of CD4+ T cells in an unbiased and efficient manner and allows detailed analysis of TCR cross-reactivity that provides recognition patterns beyond discrete peptides. We determine the cognate peptides of virus- and tumor-specific T cells in mouse disease models and present a proof of concept for human T cells. Furthermore, we use MCR to identify immunogenic tumor neo-antigens and show that vaccination with a peptide naturally recognized by tumor-infiltrating lymphocytes efficiently protects mice from tumor challenge. Thus, the MCR technology holds promise for basic research and clinical applications, allowing the personalized identification of T cell-specific neo-antigens in patients.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Kisielow J,Obermair FJ,Kopf M

doi

10.1038/s41590-019-0335-z

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

652-662

issue

5

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-019-0335-z

journal_volume

20

pub_type

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