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Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.

ABSTRACT: Recognition of self-antigens by T lymphocytes is a central event in autoimmunity. Understanding of the molecular interactions between T cell receptors (TCR) and self-epitopes may explain how T cells escape thymic education and initiate an autoimmune reaction. We have studied five human in vivo activated T cell clones specific for the region 535-551 of human thyroid peroxidase (TPO) established from a Graves' patient. Three clones (37, 72, and 73) expressed identical TCR beta and alpha chains rearranging V beta 1.1 and V alpha 15.1, and were considered sister clones. Clone 43 differed from clone 37 and its sisters in the J alpha region only. Clone NP-7 expressed V beta 6.5 but rearranged two in-frame TCR alpha chain, both using the V alpha 22.1 segment. Fine epitope mapping using nested peptides showed that clones using identical TCR beta chains, identical V alpha, but a different J alpha recognized distinct, nonoverlapping epitopes in the TPO 535-551 region. This finding shows that a different J alpha region alone leads to a heterogeneous pattern of recognition. This indicates that the "restricted" TCR V region usage sometimes found in autoimmune diseases may not always correspond to identical epitope recognition. To confirm that clones 37 (and its sisters) and 43 recognize different epitopes, the T cell clones were stimulated with a TPO-transfected autologous Epstein-Barr virus (EBV) cell line (TPO-EBV) that presents TPO epitopes afer endogenous processing. Only clone 37 and its sisters recognizes the TPO-EBV cell line, suggesting that the epitope recognized by clone 43 is not presented upon endogenous processing. We have shown that thyroid epithelial cells (TEC), the only cells that produce TPO, express HLA class II molecules in Graves' disease and can act as an antigen-presenting cells, presenting TPO after endogenous processing to autoantigen-reactive T cell clones. We tested, therefore, whether autologous TEC induced the same pattern of stimulation as TPO-EBV; T cell clone 37 recognizes the TEC, whereas it is stimulated poorly by the TPO loaded to autologous peripheral blood mononuclear cells (PBMC). Clone 43, which fails to recognize the TPO-EBV, also fails to recognize the TEC, but is activated by exogenous TPO presented by autologous PBMC. These results show that exogenous versus endogenous processing in vivo generates a different TPO epitope repertoire, producing a "cryptic" epitope (epitope not always available for recognition). Our findings define a route by which human self-reactive T cells may escape thymic selection and become activated in vivo, thus possibly leading to autoimmunity.

SUBMITTER: Quaratino S

PROVIDER: S-EPMC2192455 | biostudies-other | 1996 Feb

REPOSITORIES: biostudies-other

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Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.

Quaratino S S Feldmann M M Dayan C M CM Acuto O O Londei M M

The Journal of experimental medicine 19960201 2

Recognition of self-antigens by T lymphocytes is a central event in autoimmunity. Understanding of the molecular interactions between T cell receptors (TCR) and self-epitopes may explain how T cells escape thymic education and initiate an autoimmune reaction. We have studied five human in vivo activated T cell clones specific for the region 535-551 of human thyroid peroxidase (TPO) established from a Graves' patient. Three clones (37, 72, and 73) expressed identical TCR beta and alpha chains rea ...[more]

PMID: 8627148

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Project description:TheoryArgumentation is crucial for all academic disciplines. Nevertheless, a lack of argumentation skills among students is evident. Two core aspects of argumentation are the recognition of argument structures (e.g., backing up claims with premises, according to the Toulmin model) and the recognition of fallacies. As both aspects may be related to content knowledge, students studying different subjects might exhibit different argumentation skills depending on whether the content is drawn from their own or from a foreign subject. Therefore, we developed an instrument to measure the recognition of both argument structures and fallacies among the groups of preservice teachers and business economics students in both their respective domains (pedagogy and economics), and a neutral domain (sustainability). For the recognition of fallacies, we distinguished between congruent and incongruent fallacies. In congruent fallacies, the two aspects of argument quality, i.e., deductive validity and inductive strength, provide converging evidence against high argument quality. In incongruent fallacies, these two aspects diverge. Based on dual process theories, we expected to observe differences in the recognition of congruent and incongruent fallacies.AimsWe investigated whether these two abilities are domain-specific and whether the recognition of fallacies depends on the congruence of two aspects of argument quality.Methods267 preservice teachers and 56 business economics students participated in the study. For the recognition of argument structures, participants assigned the five statements constituting one argument to the corresponding component according to the Toulmin model. For the recognition of fallacies, we created arguments and incorporated a common fallacy into some of them: formal fallacy, overgeneralization, irrelevance, or circularity. Participants rated whether the argument was cogent or not, which was followed by a brief justification.ResultsDomain specificity could not be found for either of both abilities. For the recognition of fallacies, two dimensions were found: a congruent dimension (formal fallacies and overgeneralizations) and an incongruent dimension (irrelevance and circularity).DiscussionThe instrument measures the recognition of both argument structures and fallacies in these two groups across domains. The recognition of fallacies differs depending on whether the deductive validity and the inductive strength of the argument are equally indicative of argument quality or not.

Dataset Information

Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.

Publications

Human self-reactive T cell clones expressing identical T cell receptor beta chains differ in their ability to recognize a cryptic self-epitope.

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