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)

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_323-339 peptide (0.5 µg/mL)-treated SMCs failed to induce OT-II CD4⁺ 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: Brewer, Professor James and Garside, Professor Paul and MacRitchie, Dr Neil and Maffia, Professor Pasquale and Grassia, Dr Gianluca 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 > School of Infection & Immunity
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
52483	1	Visualising antigen presentation in mouse models of atherosclerosis	Pasquale Maffia	Medical Research Scotland (MED-SCOT)	276 FRG	III -IMMUNOLOGY