Diabetogenic T-Cell Clones Recognize an Altered Peptide of Chromogranin A

Diabetogenic T-Cell Clones Recognize an Altered Peptide of Chromogranin A

Chromogranin A (ChgA) has been identified as the antigen target for three NOD-derived, diabetogenic CD4 T-cell clones, including the well-known BDC-2.5. These T-cell clones respond weakly to the peptide WE14, a naturally occurring proteolytic cleavage product from ChgA. We show here that WE14 can be converted into a highly antigenic T-cell epitope through treatment with the enzyme transglutamin...

Cell Clones: A Central Role for TNF- Effector Function of Diabetogenic CD4 Th1 T

Effector function of diabetogenic CD4 Th1 T cell clones: a central role for TNF-alpha.

Effector function of T cells in autoimmune diabetes has been widely studied with mixed populations of lymphoid T cells stimulated ex vivo, but this approach does not permit evaluation of the contribution by a single T cell clone in the inflammatory site during pathogenesis. We have investigated cytokine production both in vitro and in vivo in a panel of diabetogenic CD4 Th1 T cell clones derive...

Structural basis for T cell recognition of altered peptide ligands: a single T cell receptor can productively recognize a large continuum of related ligands

T cells recognize short linear peptides bound to major histocompatibility complex (MHC)-encoded molecules. Subtle molecular changes in peptide antigens produce altered peptide ligands (APLs), which induce different T cell responses from those induced by the antigenic ligand. A molecular basis for how these slight molecular variations lead to such different consequences for the T cell has not be...

Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register.

A peptide derived from the insulin B chain contains a major epitope for diabetogenic CD4(+) T cells in the NOD mouse model of type 1 diabetes (T1D). This peptide can fill the binding groove of the NOD MHCII molecule, IA(g7), in a number of ways or "registers." We show here that a diverse set of NOD anti-insulin T cells all recognize this peptide bound in the same register. Surprisingly, this re...