Universität zu Köln

Schmied, Sabine, Gostick, Emma, Price, David A., Abken, Hinrich, Assenmacher, Mario and Richter, Anne (2015). Analysis of the functional WT1-specific T-cell repertoire in healthy donors reveals a discrepancy between CD4(+) and CD8(+) memory formation. Immunology, 145 (4). S. 558 - 570. HOBOKEN: WILEY. ISSN 1365-2567

Full text not available from this repository.

Abstract

The Wilms' tumour-1 (WT1) protein is considered a prime target for cancer immunotherapy based on its presumptive immunogenicity and widespread expression across a variety of malignancies. However, little is known about the naturally occurring WT1-specific T-cell repertoire because self-derived antigens typically elicit low frequency responses that challenge the sensitivity limits of current detection techniques. In this study, we used highly efficient cell enrichment procedures based on CD137, CD154, and pHLA class I tetramer staining to conduct a detailed analysis of WT1-specific T cells from the peripheral blood. Remarkably, we detected WT1-specific CD4(+) and CD8(+) T-cell populations in the vast majority of healthy individuals. Memory responses specific for WT1 were commonly present in the CD4(+) T-cell compartment, whereas WT1-specific CD8(+) T cells almost universally displayed a naive phenotype. Moreover, memory CD4(+) and naive CD8(+) T cells with specificity for WT1 were found to coexist in some individuals. Collectively, these findings suggest a natural discrepancy between the CD4(+) and CD8(+) T-cell lineages with respect to memory formation in response to a self-derived antigen. Nonetheless, WT1-specific T cells from both lineages were readily activated ex vivo and expanded in vitro, supporting the use of strategies designed to exploit this expansive reservoir of self-reactive T cells for immunotherapeutic purposes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schmied, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Gostick, Emma UNSPECIFIED UNSPECIFIED UNSPECIFIED Price, David A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Assenmacher, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Richter, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-397812
DOI:	10.1111/imm.12472
Journal or Publication Title:	Immunology
Volume:	145
Number:	4
Page Range:	S. 558 - 570
Date:	2015
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1365-2567
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WT1 PEPTIDE VACCINATION; ACUTE MYELOID-LEUKEMIA; EPITOPE SPECIFICITIES; IMMUNE-RESPONSES; FULL REPERTOIRE; ANTIGEN; VIRUS; NAIVE; TRANSPLANTATION; FREQUENCY Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/39781