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Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells

Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells
Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells

The role of micrometer-scale clustering of TCRs at the T cell-antigen-presenting cell (APC) interface in T cell activation is an area of active investigation. Here we have investigated the impact of variations in the extent of TCR clustering on the activation of naive CD4+ T cells. These T cells are derived from transgenic (tg) mice expressing TCRs (172.10 and 1934.4) specific for the N-terminal nonapeptide of MBP bound to I-Au, and are associated with murine experimental autoimmune encephalomyelitis (EAE). The 172.10 TCR has a ∼4-fold higher affinity for antigen relative to the 1934.4 TCR, allowing us to compare the properties of two tg T cells of different avidities. We observe that variations in large-scale TCR clustering at the T cell-APC interface do not correlate well with the extent of activation (CD25 or CD69 up-regulation and IL-2 or IFN-γ production). Efficient activation can also be achieved in the absence of micrometer-scale TCR clustering, indicating that this is not a prerequisite for the effective stimulation of naive T cells.

0953-8178
1615-1625
Pastor, Silvia
2a71073b-f534-4b18-8eaa-de9030d4bf27
Vaccaro, Carlos G.
f576072e-379e-4f42-9bd7-595b2f5b7d58
Minguela, Alfredo
89d0d2bb-fdfb-47ad-b925-4c0687ede7ae
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Pastor, Silvia
2a71073b-f534-4b18-8eaa-de9030d4bf27
Vaccaro, Carlos G.
f576072e-379e-4f42-9bd7-595b2f5b7d58
Minguela, Alfredo
89d0d2bb-fdfb-47ad-b925-4c0687ede7ae
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Pastor, Silvia, Vaccaro, Carlos G., Minguela, Alfredo, Ober, Raimund J. and Ward, E. Sally (2006) Analyses of TCR clustering at the T cell-antigen-presenting cell interface and its impact on the activation of naive CD4+ T cells. International Immunology, 18 (11), 1615-1625. (doi:10.1093/intimm/dxl095).

Record type: Article

Abstract

The role of micrometer-scale clustering of TCRs at the T cell-antigen-presenting cell (APC) interface in T cell activation is an area of active investigation. Here we have investigated the impact of variations in the extent of TCR clustering on the activation of naive CD4+ T cells. These T cells are derived from transgenic (tg) mice expressing TCRs (172.10 and 1934.4) specific for the N-terminal nonapeptide of MBP bound to I-Au, and are associated with murine experimental autoimmune encephalomyelitis (EAE). The 172.10 TCR has a ∼4-fold higher affinity for antigen relative to the 1934.4 TCR, allowing us to compare the properties of two tg T cells of different avidities. We observe that variations in large-scale TCR clustering at the T cell-APC interface do not correlate well with the extent of activation (CD25 or CD69 up-regulation and IL-2 or IFN-γ production). Efficient activation can also be achieved in the absence of micrometer-scale TCR clustering, indicating that this is not a prerequisite for the effective stimulation of naive T cells.

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More information

Accepted/In Press date: 27 August 2006
e-pub ahead of print date: 27 September 2006
Published date: November 2006

Identifiers

Local EPrints ID: 423583
URI: http://eprints.soton.ac.uk/id/eprint/423583
ISSN: 0953-8178
PURE UUID: c8652a15-a5b3-4fe2-8457-d01f894c1d85
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

Catalogue record

Date deposited: 27 Sep 2018 16:30
Last modified: 18 Mar 2024 03:48

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Contributors

Author: Silvia Pastor
Author: Carlos G. Vaccaro
Author: Alfredo Minguela
Author: Raimund J. Ober ORCID iD
Author: E. Sally Ward ORCID iD

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