Thyroglobulin peptides associate in vivo to HLA-DR in autoimmune thyroid glands Article

Muixí, L, Carrascal, M, Alvarez, I et al. (2008). Thyroglobulin peptides associate in vivo to HLA-DR in autoimmune thyroid glands . JOURNAL OF IMMUNOLOGY, 181(1), 795-807. 10.4049/jimmunol.181.1.795

cited authors

  • Muixí, L; Carrascal, M; Alvarez, I; Daura, X; Martí, M; Armengol, MP; Pinilla, C; Abian, J; Pujol-Borrell, R; Jaraquemada, D

authors

abstract

  • Endocrine epithelial cells, targets of the autoimmune response in thyroid and other organ-specific autoimmune diseases, express HLA class II (HLA-II) molecules that are presumably involved in the maintenance and regulation of the in situ autoimmune response. HLA-II molecules thus expressed by thyroid cells have the "compact" conformation and are therefore expected to stably bind autologous peptides. Using a new approach to study in situ T cell responses without the characterization of self-reactive T cells and their specificity, we have identified natural HLA-DR-associated peptides in autoimmune organs that will allow finding peptide-specific T cells in situ. This study reports a first analysis of HLA-DR natural ligands from ex vivo Graves' disease-affected thyroid tissue. Using mass spectrometry, we identified 162 autologous peptides from HLA-DR-expressing cells, including thyroid follicular cells, with some corresponding to predominant molecules of the thyroid colloid. Most interestingly, eight of the peptides were derived from a major autoantigen, thyroglobulin. In vitro binding identified HLA-DR3 as the allele to which one of these peptides likely associates in vivo. Computer modeling and bioinformatics analysis suggested other HLA-DR alleles for binding of other thyroglobulin peptides. Our data demonstrate that although the HLA-DR-associated peptide pool in autoimmune tissue mostly belongs to abundant ubiquitous proteins, peptides from autoantigens are also associated to HLA-DR in vivo and therefore may well be involved in the maintenance and the regulation of the autoimmune response. Copyright © 2008 by The American Association of Immunologists, Inc.

publication date

  • January 1, 2008

published in

Digital Object Identifier (DOI)

start page

  • 795

end page

  • 807

volume

  • 181

issue

  • 1