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Activated integrins identify functional antigen-specific CD8 + T cells within minutes after antigen stimulation.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jun 12; Vol. 115 (24), pp. E5536-E5545. Date of Electronic Publication: 2018 May 29. - Publication Year :
- 2018
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Abstract
- Immediate β <subscript>2</subscript> -integrin activation upon T cell receptor stimulation is critical for effective interaction between T cells and their targets and may therefore be used for the rapid identification and isolation of functional T cells. We present a simple and sensitive flow cytometry-based assay to assess antigen-specific T cells using fluorescent intercellular adhesion molecule (ICAM)-1 multimers that specifically bind to activated β <subscript>2</subscript> -integrins. The method is compatible with surface and intracellular staining; it is applicable for monitoring of a broad range of virus-, tumor-, and vaccine-specific CD8 <superscript>+</superscript> T cells, and for isolating viable antigen-reacting cells. ICAM-1 binding correlates with peptide-MHC multimer binding but, notably, it identifies the fraction of antigen-specific CD8 <superscript>+</superscript> T cells with immediate and high functional capability (i.e., expressing high levels of cytotoxic markers and cytokines). Compared with the currently available methods, staining of activated β <subscript>2</subscript> -integrins presents the unique advantage of requiring activation times of only several minutes, therefore delivering functional information nearly reflecting the in vivo situation. Hence, the ICAM-1 assay is most suitable for rapid and precise monitoring of functional antigen-specific T cell responses, including for patient samples in a variety of clinical settings, as well as for the isolation of functional T cells for adoptive cell-transfer immunotherapies.<br />Competing Interests: The authors declare no conflict of interest.<br /> (Copyright © 2018 the Author(s). Published by PNAS.)
- Subjects :
- Adolescent
Adoptive Transfer methods
Adult
Humans
Immunotherapy, Adoptive methods
Intercellular Adhesion Molecule-1 immunology
Lymphocyte Activation immunology
Receptors, Antigen, T-Cell immunology
Young Adult
Antigens immunology
CD18 Antigens immunology
CD8-Positive T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 115
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 29844168
- Full Text :
- https://doi.org/10.1073/pnas.1720714115