Chromogranin A is an autoantigen in type 1 diabetes

BD Stadinski, T Delong, N Reisdorph, R Reisdorph… - Nature …, 2010 - nature.com
BD Stadinski, T Delong, N Reisdorph, R Reisdorph, RL Powell, M Armstrong, JD Piganelli…
Nature immunology, 2010nature.com
Autoreactive CD4+ T cells are involved in the pathogenesis of many autoimmune diseases,
but the antigens that stimulate their responses have been difficult to identify and in most
cases are not well defined. In the nonobese diabetic (NOD) mouse model of type 1 diabetes,
we have identified the peptide WE14 from chromogranin A (ChgA) as the antigen for highly
diabetogenic CD4+ T cell clones. Peptide truncation and extension analysis shows that
WE14 bound to the NOD mouse major histocompatibility complex class II molecule I-Ag7 in …
Abstract
Autoreactive CD4+ T cells are involved in the pathogenesis of many autoimmune diseases, but the antigens that stimulate their responses have been difficult to identify and in most cases are not well defined. In the nonobese diabetic (NOD) mouse model of type 1 diabetes, we have identified the peptide WE14 from chromogranin A (ChgA) as the antigen for highly diabetogenic CD4+ T cell clones. Peptide truncation and extension analysis shows that WE14 bound to the NOD mouse major histocompatibility complex class II molecule I-Ag7 in an atypical manner, occupying only the carboxy-terminal half of the I-Ag7 peptide-binding groove. This finding extends the list of T cell antigens in type 1 diabetes and supports the idea that autoreactive T cells respond to unusually presented self peptides.
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