Format

Send to

Choose Destination
Brain. 2013 Jun;136(Pt 6):1783-98. doi: 10.1093/brain/awt108.

HLA-DR15-derived self-peptides are involved in increased autologous T cell proliferation in multiple sclerosis.

Author information

1
Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, Centre for Molecular Neurobiology Hamburg, University Medical Centre Eppendorf, 20251 Hamburg, Germany.

Abstract

The HLA-DR15 haplotype confers the largest part of the genetic risk to develop multiple sclerosis, a prototypic CD4+ T cell-mediated autoimmune disease. The mechanisms how certain HLA-class II molecules functionally contribute to autoimmune diseases are still poorly understood, but probably involve shaping an autoimmune-prone T cell repertoire during central tolerance in the thymus and subsequently maintaining or even expanding it in the peripheral immune system. Self-peptides that are presented by disease-associated HLA-class II molecules most likely play important roles during both processes. Here, we examined the functional involvement of the HLA-DR15 haplotype in autologous proliferation in multiple sclerosis and the contribution of HLA-DR15 haplotype-derived self-peptides in an in vitro system. We observe increased autologous T cell proliferation in patients with multiple sclerosis in relation to the multiple sclerosis risk-associated HLA-DR15 haplotype. Assuming that the spectrum of self-peptides that is presented by the two HLA-DR15 allelic products is important for sustaining autologous proliferation we performed peptide elution and identification experiments from the multiple sclerosis-associated DR15 molecules and a systematic analysis of a DR15 haplotype-derived self-peptide library. We identify HLA-derived self-peptides as potential mediators of altered autologous proliferation. Our data provide novel insights about perturbed T cell repertoire dynamics and the functional involvement of the major genetic risk factor, the HLA-DR15 haplotype, in multiple sclerosis.

KEYWORDS:

HLA-DR15; autologous T cell proliferation; homeostatic proliferation; multiple sclerosis; self-peptides

PMID:
23739916
DOI:
10.1093/brain/awt108
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for Zurich Open Access Repository and Archive
Loading ...
Support Center