Epitopes described in "Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes."

Article Authors:Michael B A Oldstone; Kurt H Edelmann; Dorian B McGavern; Justin T Cruite; Megan J Welch
Article Title:Molecular anatomy and number of antigen specific CD8 T cells required to cause type 1 diabetes.
Reference Detail
Reference ID:1025322
Abstract:We quantified CD8 T cells needed to cause type 1 diabetes and studied the anatomy of the CD8 T cell/beta () cell interaction at the immunologic synapse. We used a transgenic model, in situ tetramer staining to distinguish antigen specific CD8 T cells from total T cells infiltrating islets and a variety of viral mutants selected for functional deletion(s) of various CD8 T cell epitopes. Twenty percent of CD8 T cells in the spleen were specific for all immunodominant and subdominant viral glycoprotein (GP) epitopes. CTLs to the immunodominant LCMV GP33-41 epitope accounted for 63% of the total (12.5% of tetramers). In situ hybridization analysis demonstrated only 1 to 2% of total infiltrating CD8 T cells were specific for GP33 CD8 T cell epitope, yet diabetes occurred in 94% of mice. The immunologic synapse between GP33 CD8 CTL and cell contained LFA-1 and perforin. Silencing both immunodominant epitopes (GP33, GP276-286) in the infecting virus led to a four-fold reduction in viral specific CD8 CTL responses, negligible lymphocyte infiltration into islets and absence of diabetes.
Affiliations:Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, United States of America. mbaobo@scripps.edu.
Reference Type:Literature
PubMed ID:23209415
Journal:PLoS Pathog
Journal Volume:8
Article Pages:e1003044
Journal ISSN:1553-7374
Article Chemical List:Immunodominant Epitopes;Receptors, Antigen, T-Cell, alpha-beta
Article MeSH List:Animals; CD8-Positive T-Lymphocytes(immunology; pathology); Diabetes Mellitus, Experimental(genetics; immunology; pathology); Diabetes Mellitus, Type 1(genetics; immunology; pathology); Immunodominant Epitopes(genetics; immunology); Immunological Synapses(genetics; immunology); Insulin-Secreting Cells(immunology; pathology); Mice; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta(genetics; immunology)
Curation Last Updated:2016-01-08 22:10:39