Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Investigating the relevance of enterovirus-specific CD8 T cell immunity in Type 1 diabetes (#77)

Martin Eichmann 1 , Robin R Knight 1 , Sami Oikarinen 2 , Heikki Hyoty 2 , Mark Peakman 1
  1. Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
  2. Department of Virology, University of Tampere, Tampere, Finland

Inheritance of Type 1 diabetes (T1D) associated-risk alleles at certain genetic loci is unable to completely account for either the onset or acceleration of Type 1 diabetes (T1D). Increasing evidence suggests that environmental factors are key triggers that contribute to disease onset. Notably, in a recent study, infection with the Coxsackievirus B1 (CBV1) serotype has been linked to T1D progression in a large prospective birth cohort study1 . CD8 T lymphocytes represent a major component of anti-viral adaptive immune responses, but are poorly understood in relation to enterovirus infection and T1D. To address this, we used in silico peptide prediction algorithms to generate a candidate list of 107 peptides with high predicted scores for presentation by HLA-A*0201. We then used sensitive CD8 IFN-gamma ELISPOT studies on CBV1-seropositive donors to screen these candidates in peptide pools and identify several novel candidate CD8 T cell peptide targets derived from CBV1. Following co-culture of peptide-pulsed dendritic cells we generated CD8 T cell lines and subsequently clones directed against these putative targets. Thus our study confirms the presence of peripheral CBV1-specific effector CD8 T cells directed against novel, CVB1-restricted epitopes in CVB1-experienced subjects. CBV1-specific CD8 T cell clones will elucidate the natural processing of these by target cells and enable peptide-HLA multimer studies to monitor peripheral numbers of circulating CBV1-specific CD8 T cells for the first time. 

  1. Laitinen, O. H., H. Honkanen, O. Pakkanen, S. Oikarinen, M. M. Hankaniemi, H. Huhtala, T. Ruokoranta, V. Lecouturier, P. Andre, R. Harju, S. M. Virtanen, J. Lehtonen, J. W. Almond, T. Simell, O. Simell, J. Ilonen, R. Veijola, M. Knip and H. Hyoty (2013). "Coxsackievirus B1 Is Associated With Induction of beta-Cell Autoimmunity That Portends Type 1 Diabetes." Diabetes.