Complexity of human immune response profiles for CD4+ T cell epitopes from the diabetes autoantigen GAD65

Autoimmunity
S A MasewiczG T Nepom

Abstract

Complex protein antigens contain multiple potential T cell recognition epitopes, which are generated through a processing pathway involving partial antigen degradation via proteases, binding to MHC molecules, and display on the APC surface, followed by recognition via the T cell receptor. We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM. Using sets of 20-mer peptides spanning the GAD65 molecule, multiple immunostimulatory epitopes were identified, with diverse class II DR molecules functioning as the restriction element. The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. Antigen-specific T cell clones and lines were derived from peripheral blood samples of pre-diabetic and IDDM patients and T cell recognition and response were measured. Highly variable proliferative and cytokine release profiles were observed, even among T cells specific for a single GAD65 epitope.

References

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Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·G T NepomB S Nepom

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Citations

Feb 14, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Gerald T Nepom
May 25, 2002·Tissue Antigens·S A MasewiczGerald T Nepom
Jun 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·John A GebeGerald T Nepom

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