T Cell activation by coxsackievirus B4 antigens in type 1 diabetes mellitus: evidence for selective TCR V  usage without superantigenic activity

Varela-Calvino, R., Sgarbi, G., Wedderburn, L. R., Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462, Tremble, J. and Peakman, M. 2001. T Cell activation by coxsackievirus B4 antigens in type 1 diabetes mellitus: evidence for selective TCR V  usage without superantigenic activity. The Journal of Immunology 167 (6) , pp. 3513-3520. 10.4049/jimmunol.167.6.3513

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Abstract

Numerous clinical and epidemiological studies link enteroviruses such as the Coxsackie virus group with the autoimmune disease type 1 diabetes mellitus (DM). In addition, there are reports that patients with type 1 DM are characterized by skewing of TCR Vβ chain selection among peripheral blood and intraislet T lymphocytes. To examine these issues, we analyzed TCR Vβ chain-specific up-regulation of the early T cell activation marker, CD69, on CD4 T cells after incubation with Coxsackievirus B4 (CVB4) Ags. CD4 T cells bearing the Vβ chains 2, 7, and 8 were the most frequently activated by CVB4. Up-regulation of CD69 by different TCR families was significantly more frequent in new onset type 1 DM patients (p = 0.04), 100% of whom (n = 8) showed activation of CD4 T cells bearing Vβ8, compared with 50% of control subjects (n = 8; p = 0.04). T cell proliferation after incubation with CVB4 Ags required live, nonfixed APCs, suggesting that the selective expansion of CD4 T cells with particular Vβ chains resulted from conventional antigen processing and presentation rather than superantigen activity. Heteroduplex analysis of TCR Vβ chain usage after CVB4 stimulation indicated a relatively polyclonal, rather than oligo- or monoclonal response to viral Ags. These results provide evidence that new-onset patients with type 1 DM and healthy controls are primed against CVB4, and that CD4 T cell responses to the virus have a selective TCR Vβ chain usage which is driven by viral Ags rather than a superantigen.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Last Modified:	27 Oct 2022 08:53
URI:	https://orca.cardiff.ac.uk/id/eprint/63664

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