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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    • "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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    • "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] "

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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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