||Monday, September 4, 2017 (17:00 – onward)
||Medium-size Conference Room, IDAC Center for Clinical Aging Research 1F
||T cell repertoire selection in the thymus
||Dept. of Immunology, Graduate School of Medicine, The University of Tokyo
||Koetsu Ogasawara (Department of Immunobiology ext.8579)
||The thymus is an organ for T cell repertoire selection. Cortical thymic epithelial cells possess unique protein degradation machinery such as thymoproteasome, which produces a unique set of MHC-bound self-peptides and thereby control positive selection of T cells. Here we found that human PSMB11 gene, which encodes a thymmoproteasome subunit, has many ‘loss-of-function’ variations at high frequency. These PSMB11 variations alter the CD8 T cell selection in mice, and one of them is associated with a risk of an autoimmune disease in human. Our findings suggest that, in addition to the MHC haplotype, antigen peptide-processing variation exerts a significant influence on T cell repertoire selection and disease susceptibility.