Murine aortic smooth muscle cells acquire, though fail to present exogenous protein antigens on major histocompatibility complex class II molecules

Maddaluno, M., MacRitchie, N., Grassia, G., Ialenti, A., Butcher, J. P., Garside, P. , Brewer, J. M. and Maffia, P. (2014) Murine aortic smooth muscle cells acquire, though fail to present exogenous protein antigens on major histocompatibility complex class II molecules. BioMed Research International(949845), (doi:10.1155/2014/949845) (PMID:25136640) (PMCID:PMC4127268)

Maddaluno, M., MacRitchie, N., Grassia, G., Ialenti, A., Butcher, J. P., Garside, P. , Brewer, J. M. and Maffia, P. (2014) Murine aortic smooth muscle cells acquire, though fail to present exogenous protein antigens on major histocompatibility complex class II molecules. BioMed Research International(949845), (doi:10.1155/2014/949845) (PMID:25136640) (PMCID:PMC4127268)

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Abstract

In atherosclerosis, vascular smooth muscle cells (SMCs) express class II major histocompatibility complex molecules (MHC class II) however, their ability to act as antigen presenting cells remains controversial. In the present study aortic murine SMC antigen presentation capacity was evaluated using the Ealpha (Eα)-GFP/Y-Ae system to visualize antigen uptake through a GFP tagged and tracking of Eα peptide/MHCII presentation using the Y-Ae Ab. Stimulation with IFN-γ (100 ng/mL) for 72 h caused a significant (<i>P</i><0.01) increase in the percentage of MHC class II positive SMCs, compared with unstimulated cells. Treatment with Eα-GFP (100 µg/mL) for 48 h induced a significant (<i>P</i><0.05) increase in the percentage of GFP positive SMCs while it did not affect the percentage of Y-Ae positive cells, being indicative of antigen uptake without its presentation in the context of MHC class II. After IFN-γ-stimulation, ovalbumin (OVA, 1 mg/mL)- or OVA<sub>323-339</sub> peptide (0.5 µg/mL)-treated SMCs failed to induce OT-II CD4<sup>+</sup> T cell activation/proliferation; this was also accompanied by a lack of expression of key costimulatory molecules (OX40L, CD40, CD70 and CD86) on SMCs. Finally, OVA-treated SMCs failed to induce DO11.10-GFP hybridoma activation, a process independent of costimulation. Our results demonstrate that while murine primary aortic SMCs express MHC class II and can acquire exogenous antigens, they fail to activate T cells through a failure in antigen presentation and a lack of costimulatory molecule expression.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Brewer, Professor James and Garside, Professor Paul and Grassia, Dr Gianluca and MacRitchie, Mr Neil and Butcher, Mr John
Authors: Maddaluno, M., MacRitchie, N., Grassia, G., Ialenti, A., Butcher, J. P., Garside, P., Brewer, J. M., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:BioMed Research International
Publisher:Hindawi Publishing Corporation
ISSN:2314-6133
ISSN (Online):2314-6141
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in BioMed Research International
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
524831Visualising antigen presentation in mouse models of atherosclerosisPasquale MaffiaMedical Research Scotland (MED-SCOT)276 FRGIII -IMMUNOLOGY