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S Guerder

Publications and source records attributed to S Guerder.

4 recordsLinked to original sources
PubMed1992

A fail-safe mechanism for maintaining self-tolerance.

Using cytotoxic T lymphocyte (CTL) responses to the class I histocompatibility antigen Qa1 and to the minor histocompatibility antigen H-Y, we show that the immune system maintains a peripheral screening process that is able to tolerize a wide variety of potentially autoimmune CTL. The critical factor is the presence or absence of specific T helper cells. If T help is available, CTL precursors that recognize antigen are activated. In the absence of help, they are tolerized. Thus, T helper cells are guardians of peripheral tolerance in CTL.

Animals↗
PubMed1989

Qa-1 restricted recognition of foreign antigen by a gamma delta T-cell hybridoma.

Distinct T-lymphocyte subsets recognize antigens in conjunction with different classes of major histocompatibility complex (MHC) glycoproteins using the T-cell receptor (TCR), a disulphide-linked heterodimer associated with the CD3 complex on the cell surface. In general, class I and class II MHC products provide a context for the recognition of foreign antigens by CD8+ and CD4+ T cells, respectively. This recognition seems to be largely dependent on alpha beta TCR heterodimers, whereas the function of the second gamma delta TCR, present on a minor subpopulation of cells, is still unknown. In the mouse, the existence of six cell-surface MHC class I products (K, D, L, Qa-1, Qa-2 and Tla) has been firmly established by serological, biochemical and genetic evidence. So far, only the most polymorphic of them, K, D and L ('classical' class I) have been reported as restriction elements for T-cell recognition of foreign antigens. The function of the relatively invariant Qa and Tla molecules remains unknown. We have made a T-helper cell hybridoma clone (DGT3) that recognizes synthetic copolymer poly(Glu50Tyr50) in the context of Qa-1 cell surface product, and has a CD4-CD8- phenotype. Our studies indicate that DGT3 cells express the gamma delta TCR on the cell surface, implicating its role in Qa-1-restricted antigen recognition. This is the first evidence that T cells can recognize foreign antigen in association with self Qa product, confirming that Qa molecules not only topologically, but also functionally, belong to the MHC.

Animals↗
PubMed1989

Does T-cell tolerance require a dedicated antigen-presenting cell?

Almost 30 years ago Burnet proposed that the immune system maintained self-tolerance by deleting autoreactive lymphocytes. Recently it has become clear that for T cells this step occurs in the thymus, where developing T cells first express their antigen-specific receptors. Here a T-cell which encounters its antigen disappears--if it is not dead, it at least stops expressing its receptors. In the periphery by contrast, encounter with antigen leads to activation and proliferation of the responding T-cell. There are two possible explanations for this difference. Either the antigen-presenting cells in the thymus are different from those in the periphery and instead of producing positive signals they directly or indirectly kill the thymocytes; or the T cells themselves are different, and like immature B cells, may die after encounter with antigen. We tested the first possibility and found that dendritic cells from spleen, which are the most potent activators of mature T cells, are also the most potent inactivators of young developing T cells. Thus it is not the antigen-presenting cell which determines whether a T-cell responds or dies, but the T-cell itself or its thymic environment.

Animals↗