Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide

Viret, Christophe; He, Xin; Janeway, Charles A.

doi:10.1073/pnas.161274698

Cited by 17 publications

(15 citation statements)

References 64 publications

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“…In contrast, our view is that the same linear sequence can be presented in two conformational states dictated by the site of assembly in the APC: in a late processing vesicle, H2-DM imparts a fixed conformer; whereas without H2-DM loading of peptide in a recycling vesicle allows for a more flexible conformer (4). We also suggest that the report of Viret et al (30) of positive selection mediated by a covalent complex of MHC and agonist peptide might be explained by similar conformation-dependent T cell reactivity.…”

Section: Discussionsupporting

confidence: 69%

APCs Present Aβk-Derived Peptides That Are Autoantigenic to Type B T Cells

Lovitch

Walters

Gross

et al. 2003

The Journal of Immunology

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Type B T cells recognize peptide provided exogenously but are ignorant of the same epitope derived from intracellular processing. In this study, we demonstrate the existence of type B T cells to an abundant autologous peptide derived from processing of the I-Ak β-chain. T cell hybridomas raised against this peptide fail to recognize syngeneic APC despite abundant presentation of the naturally processed epitope but react in a dose-dependent manner to exogenous peptide. Moreover, these hybridomas respond to Aβk peptide extracted from the surface of I-Ak-expressing APC. This peptide was isolated from B cell lines where it was found in high abundance; it was also present in lines lacking HLA-DM, but in considerably lower amounts. Therefore, type B T cells exist in the naive repertoire to abundant autologous peptides. We discuss the implications of these findings to the potential biological role of type B T cells in immune responses and autoimmune pathology.

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Section: Discussionsupporting

confidence: 69%

APCs Present Aβk-Derived Peptides That Are Autoantigenic to Type B T Cells

Lovitch

Walters

Gross

et al. 2003

The Journal of Immunology

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“…A natural ligand defined for positive selection of the N15 VSV-virusspecific TCR was also an agonist ligand [4]. Extensive discussion continues to evolve around whether a selecting ligand is an agonist or antagonist [1,[31][32][33]. This, however, is a moot point for several reasons.…”

Section: Discussionmentioning

confidence: 99%

Weak agonist self‐peptides promote selection and tuning of virus‐specific T cells

et al. 2003

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Recent progress has begun to define the interactions and signaling pathways that are triggered during positive selection. To identify and further examine self-peptides that can mediate positive selection, we searched a protein-database to find peptides that have minimal homology with the viral peptide (p33) that activates a defined P14 transgenic TCR. We identified four peptides that could bind the restriction element H-2D b and induce proliferation of P14 transgenic splenocytes at high concentration. Two of the four peptides (DBM and RPP) were able to positively select the virus-specific TCR in fetal thymic organ culture but were unable to induce clonal deletion. Reverse-phase HPLC and mass spectrometry demonstrated that these peptides were presented by H-2D b molecules on thymic epithelial cell lines. We also examined whether the selecting ligands altered T cell responsiveness in vitro. DBM-selected T cells lost their ability to respond to the positively selecting ligand DBM, whereas RPP-selected T cells only retained their ability to respond to high concentrations of RPP. These results demonstrate that self-peptides that mediate positive selection can differentially "tune" the activation threshold of T cells and alter the functional repertoire of T cells.

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“…Therefore, we feel that the explanation of the higher T hybridoma response to A b wt+A b Ep than to A b Ep cells may lie in a contribution of weak TCR interaction with bystander peptides that are similar or identical to those involved in the positive selection of T lymphocytes from which these hybridomas originated. Several investigators have shown that agonist peptides can promote the positive selection of T lymphocytes in vivo [18,19], especially when presented in low concentrations. Low-affinity self-reactive T cell clones may escape negative selection and peripheral tolerance [20,21], and such clones might have given rise to our hybridomas.…”

Section: Resultsmentioning

confidence: 99%

The specific T-cell response to antigenic peptides is influenced by bystander peptides

Nowak

Pajtasz‐Piasecka

Chmielowski

et al. 2006

Cellular and Molecular Biology Letters

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T lymphocytes recognize antigens in the form of peptides presented by major histocompatibility complex (MHC) molecules on the cell surface. Only a small proportion of MHC class I and class II molecules are loaded with foreign antigenic peptides; the vast majority are loaded with thousands of different self peptides. It was suggested that MHC molecules presenting self peptides may serve either to decrease (antagonistic effect) or increase (synergistic effect) the T cell response to a specific antigen. Here, we present our finding that transfected mouse fibroblasts presenting a single antigenic peptide covalently bound to a class II MHC molecule stimulated specific mouse T cell hybridoma cells to an interleukin-2 response less efficiently than fibroblasts presenting a similar amount of antigenic peptide in the presence of class II molecules loaded with heterogenous bystander peptides.

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Paradoxical intrathymic positive selection in mice with only a covalently presented agonist peptide

Cited by 17 publications

References 64 publications

APCs Present Aβk-Derived Peptides That Are Autoantigenic to Type B T Cells

APCs Present Aβk-Derived Peptides That Are Autoantigenic to Type B T Cells

Weak agonist self‐peptides promote selection and tuning of virus‐specific T cells

The specific T-cell response to antigenic peptides is influenced by bystander peptides

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