Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells

Abstract

The first step in the induction of immune responses, whether humoral or cell mediated, requires the interaction between antigen-presenting cells and T lymphocytes restricted at the major histocompatibility complex (MHC). These cells invariably express MHC class II molecules (HLA-D region in man and Ia in mouse) which are recognized by T cells of the helper/inducer subset in association with antigen fragments. Interestingly, in certain pathological conditions, for example in autoimmune diseases such as thyroiditis and diabetic insulitis, class II molecules may be expressed on epithelial cells that normally do not express them. We speculated that these cells may be able to present their surface autoantigens to T cells, and that this process may be crucial to the induction and maintenance of autoimmunity. A critical test of this hypothesis would be to determine whether epithelial cells bearing MHC class II molecules (class II+ cells) can present antigen to T cells. We report here that class II+ thyroid follicular epithelial cells (thyrocytes) can indeed present viral peptide antigens to cloned human T cells.

Up‐regulation of class II major histocompatibility complex and intercellular adhesion molecule 1 expression on scleroderma fibroblasts and endothelial cells by interferon‐γ and tumor necrosis factor α in the early disease stage

“…Other functions of class I1 MHC antigens include selection of mature class II-restricted CD4+ T lymphocytes in the thymus, class I1 MHC-incompatible graft rejection, and transmembrane signaling due to the activation of Iaexpressing cells (39). These functions account for the central role played by class I1 MHC molecules in T cell-dependent immune responses, and emphasize the potential importance of aberrant class I1 antigen expression in autoimmune diseases (16,17,40).…”

Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease

“…The inflammatory cell infiltration observed in some tissues of homozygous mutant animals resembles to a variable degree that seen in certain human autoimmune diseases such as myocarditis, polymyositis 31 , and Sjogren's syndrome 32 , Pathological autoreactivity has been attributed to several processes in which TGF-β1 may playa regulatory role, including dysfunction of T cell suppression and aberrant expression of major histocompatibility complex (MHC) antigen by cells that normally do not present antigen [33][34][35] . TGF-β1 administration to mice protects against collagen-induced arthritis and relapsing experimental allergic encephalomyelitis [36][37][38][39] .…”

Expression of MHC products and leucocyte differentiation antigens in gynaecological neoplasms: An immunohistological analysis of the tumour cells and infiltrating leucocytes

“…In both autoimmune and neoplastic diseases MHC Class II products on target cells are envisaged as a vehicle for the presentation of autoantigen to T helper/inducer lymphocytes on the assumption that the configuration of the particular Class II product fits that of the autoantigen (Londei et al, 1984). In malignant melanoma, for instance, autologous lymphoproliferative responses can be induced by DR-positive tumour cells (Guerry et al, 1984) (Ortaldo et al, 1981), the LGL population was monitored in sections with two McAbs, one of which (B73.1) is reactive with virtually the entire LGL population (Perussia et al, 1983a,b) and another (Leu 7; HNK1) which reacts with approximately 75% of LGL as well as a subset of T (suppressor) cells (Abo & Balch, 1981;Abo et al, 1982a,b).…”