Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis Article

Zhang, X, Tang, Y, Sujkowska, D et al. (2008). Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: Implications for the initiation of the autoimmune response in multiple sclerosis . 38(5), 1297-1309. 10.1002/eji.200737519

cited authors

  • Zhang, X; Tang, Y; Sujkowska, D; Wang, J; Ramgolam, V; Sospedra, M; Adams, J; Martin, R; Pinilla, C; Markovic-Plese, S

authors

abstract

  • TCR degeneracy may facilitate self-reactive T cell activation and the initiation of an autoimmune response in multiple sclerosis (MS). MHC class II alleles of the DR2 haplotype DR2a (DRB5*0101) and DR2b (DRB1*1501) are associated with an increased risk for MS in Caucasian populations. In order to selectively expand and characterize T cells with a high degree of TCR degeneracy that recognize peptides in the context of disease-associated DR2 alleles, we developed DR2-anchored peptide mixtures (APM).We report here that DR2-APM have a high stimulatory potency and can selectively expand T cells with a degenerate TCR (TCRdeg). Due to the low concentration of individual peptides in the mixtures, T cell clones' proliferative response to DR2-APM implies that multiple peptides stimulate the TCR, which is a characteristic of TCRdeg. The frequency of DR2-APM-reactive T cells is significantly higher in MS patients than in healthy controls, suggesting that they may play a role in the development of the autoimmune response in MS. DR2-APM-reactive cells have a dual DR2 restriction: they recognize DR2-APM in the context of both DR2a and DR2b molecules. The DR2-APM-reactive cells' IL-17 secretion, together with cross-reactivity against myelin peptides, may contribute to their role in the development of autoimmune response in MS. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

publication date

  • May 1, 2008

Digital Object Identifier (DOI)

start page

  • 1297

end page

  • 1309

volume

  • 38

issue

  • 5