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HLA-DR15-derived self-peptides are involved in increased autologous T cell proliferation in multiple sclerosis.
- Source :
- Brain: A Journal of Neurology; Jun2013, Vol. 136 Issue 6, p1783-1798, 16p
- Publication Year :
- 2013
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00068950
- Volume :
- 136
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Brain: A Journal of Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 88148233
- Full Text :
- https://doi.org/10.1093/brain/awt108