Format

Send to

Choose Destination
Mol Cell Proteomics. 2015 Aug;14(8):2085-102. doi: 10.1074/mcp.M114.045690. Epub 2015 May 19.

A Combined Omics Approach to Generate the Surface Atlas of Human Naive CD4+ T Cells during Early T-Cell Receptor Activation.

Author information

1
From the ‡Center of Allergy and Environment (ZAUM), Technische Universität und Helmholtz Zentrum München, Munich, Germany;
2
§Research Unit Protein Science, Helmholtz Zentrum München, Neuherberg, Germany;
3
¶Department of Informatics, Bioinformatics & Computational Biology i12, Technische Universität München, Garching/Munich, Germany; ‖New York Consortium on Membrane Protein Structure (NYCOMPS), New York Structural Biology Center, New York, New York 10027;
4
¶Department of Informatics, Bioinformatics & Computational Biology i12, Technische Universität München, Garching/Munich, Germany; **TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), Technische Universität München, Munich, Germany;
5
‡‡Institute of Virology, Helmholtz Zentrum München, Neuherberg, Germany;
6
‡‡Institute of Virology, Helmholtz Zentrum München, Neuherberg, Germany; §§Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, Tübingen, Germany;
7
¶¶Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany;
8
From the ‡Center of Allergy and Environment (ZAUM), Technische Universität und Helmholtz Zentrum München, Munich, Germany; ‖‖DZL- Member of the German Lung Research Center.
9
From the ‡Center of Allergy and Environment (ZAUM), Technische Universität und Helmholtz Zentrum München, Munich, Germany; ‖‖DZL- Member of the German Lung Research Center Kathrin.Suttner@lrz.tum.de.

Abstract

Naive CD4(+) T cells are the common precursors of multiple effector and memory T-cell subsets and possess a high plasticity in terms of differentiation potential. This stem-cell-like character is important for cell therapies aiming at regeneration of specific immunity. Cell surface proteins are crucial for recognition and response to signals mediated by other cells or environmental changes. Knowledge of cell surface proteins of human naive CD4(+) T cells and their changes during the early phase of T-cell activation is urgently needed for a guided differentiation of naive T cells and may support the selection of pluripotent cells for cell therapy. Periodate oxidation and aniline-catalyzed oxime ligation technology was applied with subsequent quantitative liquid chromatography-tandem MS to generate a data set describing the surface proteome of primary human naive CD4(+) T cells and to monitor dynamic changes during the early phase of activation. This led to the identification of 173 N-glycosylated surface proteins. To independently confirm the proteomic data set and to analyze the cell surface by an alternative technique a systematic phenotypic expression analysis of surface antigens via flow cytometry was performed. This screening expanded the previous data set, resulting in 229 surface proteins, which were expressed on naive unstimulated and activated CD4(+) T cells. Furthermore, we generated a surface expression atlas based on transcriptome data, experimental annotation, and predicted subcellular localization, and correlated the proteomics result with this transcriptional data set. This extensive surface atlas provides an overall naive CD4(+) T cell surface resource and will enable future studies aiming at a deeper understanding of mechanisms of T-cell biology allowing the identification of novel immune targets usable for the development of therapeutic treatments.

PMID:
25991687
PMCID:
PMC4528239
DOI:
10.1074/mcp.M114.045690
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center