HLA-DM and invariant chain are expressed by thyroid follicular cells, enabling the expression of compact DR molecules

Unitat d'Immunologia, Hospital Universitari Germans Trias i Pujol, Bellaterra, Barcelona, Spain.
International Immunology (Impact Factor: 2.54). 03/1999; 11(2):269-77. DOI: 10.1093/intimm/11.2.269
Source: PubMed


Thyroid follicular cells (TFC) in Graves' disease (GD) hyperexpress HLA class I and express ectopic HLA class II molecules, probably as a consequence of cytokines produced by infiltrating T cells. This finding led us to postulate that TFC could act as antigen-presenting cells, and in this way be responsible for the induction and/or maintenance of the in situ autoimmune T cell response. Invariant chain (li) and HLA-DM molecules are implicated in the antigen processing and presentation by HLA class II molecules. We have investigated the expression of these molecules by TFC from GD glands. The results demonstrate that class II+ TFC from GD patients also express li and HLA-DM, and this expression is increased after IFN-gamma stimulation. The level of HLA-DM expression by TFC was low but sufficient to catalyze peptide loading into the HLA class II molecules and form stable HLA class II-peptide complexes expressed at the surface of TFC. These results have implications for the understanding of the possible role of HLA class II+ TFC in thyroid autoimmune disease.

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Available from: Dolores Jaraquemada, Oct 07, 2015
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    • "There is very high expression of MHC-II in autoimmune TFC, whereas class II expression in pancreatic islets in diabetes is not so clear, despite the stronger association to HLA-DR and -DQ alleles with T1D compared to thyroid autoimmunity (65). HLA-DM is also expressed by autoimmune TFC, although at lower levels than in conventional APCs (66). In the absence of DM or if DM is insufficient, high affinity peptides may be outcompeted by low-affinity peptides. "
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    ABSTRACT: T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions.
    Frontiers in Immunology 12/2013; 4:442. DOI:10.3389/fimmu.2013.00442
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    • "Thyrocytes may produce HLA I under the influence of cytokines of lymphocytes present in the thyroid. In this way, the autoimmunologic reaction is sustained [Catalfamo et al., 1999] "
    Autoimmune Disorders - Pathogenetic Aspects, 10/2011; , ISBN: 978-953-307-643-0
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    • "A more refined analysis will be required to determine the putative APCs presenting each peptide, but the use of whole tissue samples has advantages, since it has provided complementary information on the tissue milieu. In addition, separation of TFC from the digested tissue requires a minimum of 24 h of culture (Catalfamo et al., 1999; Roura-Mir et al., 1997; Sospedra et al., 1995) that induces downregulation of class II expression, protein degradation, and maybe the modification of the peptide repertoire. Moreover , the yield of thyroid cells obtained from these cultures is low making the use of single-cell-type samples not feasible. "
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    ABSTRACT: The association of the major histocompatibility complex (MHC) genes with autoimmune diseases together with the ectopic expression of class II molecules by epithelial cells of the target tissue gives to these molecules a central role in the pathogenesis of the disease, in its regulation and in the persistence of the immune response in situ. HLA-DR molecules expressed by thyroid follicular cells in thyroid autoimmune diseases are compact molecules stably associated with peptides. The nature of these peptides is of vital importance in the understanding of the disease, since these MHC-II-peptide complexes are going to be recognized by both effector and regulatory T cells in situ. In this chapter, we review the current state of the analysis of naturally processed peptides presented by MHC class II molecules in the context of autoimmunity and we discuss our data of natural HLA-DR ligands eluted from Graves' disease affected thyroid glands, from where autoantigen-derived peptides have been identified.
    Advances in Immunology 02/2008; 99:165-209. DOI:10.1016/S0065-2776(08)00606-8 · 5.96 Impact Factor
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