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Proteomics. 2018 Jun;18(12):e1700410. doi: 10.1002/pmic.201700410. Epub 2018 Apr 18.

T-Cell Immunopeptidomes Reveal Cell Subtype Surface Markers Derived From Intracellular Proteins.

Author information

1
Department of Chemical and Systems Biology, Stanford Medicine, Stanford, CA, USA.
2
Department of Pediatrics, Division of Hematology Oncology, Stanford Medicine and Lucille Packard Children's Hospital, Stanford, CA, USA.
3
Department of Medicine, Division of Oncology, Stanford Medicine, Stanford, CA, USA.
4
Department of Medicine, Division of Hematology, University of California, San Francisco, San Francisco, CA, USA.

Abstract

Immunopeptidomes promise novel surface markers as ideal immunotherapy targets, but their characterization by mass spectrometry (MS) remains challenging. Until recently, cell numbers exceeding 109 were needed to survey thousands of HLA ligands. Such limited analytical sensitivity has historically constrained the types of clinical specimens that can be evaluated to cell cultures or bulk tissues. Measuring immunopeptidomes from purified cell subpopulations would be preferable for many applications, particularly those evaluating rare, primary hematopoietic cell lineages. Here, we test the feasibility of immunopeptidome profiling from limited numbers of primary purified human regulatory T cells (TReg ), conventional T cells (Tconv ), and activated T cells. The combined T cell immunopeptide dataset reported here contains 13 804 unique HLA ligands derived from 5049 proteins. Of these, more than 700 HLA ligands were derived from 82 proteins that we exclusively identified from TReg -enriched cells. This study 1) demonstrates that primary, lineage-enriched T cell subpopulations recovered from single donors are compatible with immunopeptidome analysis; 2) presents new TReg -biased ligand candidates; and 3) supports immunopeptidome surveys' value for revealing T cell biology that may not be apparent from expression data alone. Taken together, these findings open up new avenues for targeting TReg and abrogating their suppressive functions to treat cancer.

KEYWORDS:

FOXP3; MHC; T cells; antigen presentation; mass spectrometry

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