LAUSR

Significance The exact autoimmune mechanism responsible for causing Type 1 diabetes (T1D) remains unknown, but is thought to be a result of autoimmune activation by some potent self-antigen. A recent work isolated a unique cell set, termed the X-cell, that displays both T cell receptors (TCR) and B cell receptors (BCR) and encodes an autoantigen that produces a strong immune response in cells from T1D patients. Here, we explored the presentation of the autoantigen mutants to the HLA-TCR immune complex with a combined theoretical and experimental approach and identified several mutated sequences that modify HLA-antigen-TCR binding and therefore change immune responses. Specifically, we identify mutants that bind more strongly to the HLA and hold relevance to unique T1D immunotherapies.