Rare, Structurally Homologous Self-Peptides Promote Thymocyte Positive Selection

Santori, Fabio R.; Kieper, William C.; Brown, Stuart M.; Lu, Yuanyao; Neubert, Thomas A.; Johnson, Kenneth L.; Naylor, Stephen; Vukmanović, Stanislav; Hogquist, Kristin A.; Jameson, Stephen C.

doi:10.1016/s1074-7613(02)00361-8

Cited by 87 publications

(118 citation statements)

References 54 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…MHC-bound self-peptides influence development of immature thymocytes (42,43), and mature T cells interact with Ags from foreign pathogens presented by self-MHC or self-peptides presented by foreign MHC molecules. The alloreactive T cells can originate from both naive and memory T cell populations (44).…”

Section: Discussionmentioning

confidence: 99%

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

Whitelegg

Oosten²,

Jordan³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Alloreactive T cells are involved in injurious graft rejection and graft-vs-host disease. However, they can also evoke beneficial responses to tumor Ags restricted by foreign MHC molecules. Manipulation of these alloreactivities requires information on the basis of T cell allorecognition. The vigorous T cell response to foreign MHC molecules may arise from peptide-independent recognition of polymorphic residues of foreign MHC molecules or peptide-specific recognition of novel peptides presented by foreign MHC molecules. We investigated CD8+ T cell allorecognition using recombinant HLA class I/peptide complexes. Peptide-specific allorecognition was examined using tetramers of HLA-A*0201 representing five peptides derived from ubiquitously expressed self-proteins that are known to bind endogenously to HLA-A*0201. Distinct subsets of CD8+ T cells specific for each HLA-A*0201/peptide combination were detected within four in vitro-stimulated T cell populations specific for foreign HLA-A*0201. Peptide-independent allorecognition was investigated using artificial Ag-presenting constructs (aAPCs) coated with CD54, CD80, and functional densities of a single HLA-A*0201/peptide combination for four different peptides. None of the four T cell populations specific for foreign HLA-A*0201 were stimulated by the aAPCs, whereas they did produce IFN-γ upon stimulation with cells naturally expressing HLA-A*0201. Thus, aAPCs did not stimulate putative peptide-independent allorestricted T cells. The results show that these alloreactive populations comprise subsets of T cells, each specific for a self-peptide presented by foreign class I molecules, with no evidence of peptide-independent components.

show abstract

Section: Discussionmentioning

confidence: 99%

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

Whitelegg

Oosten²,

Jordan³

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…To ensure that only those cells that express TCRs with the appropriate specificities are allowed to mature, DP thymocytes are subjected to a selection process on the basis of their TCR specificity for peptideþMHC that promotes the survival and differentiation of functionally competent cells ( positive selection) and triggers the deletion of overtly autoreactive cells (negative selection) (Sebzda et al 1999;Starr et al 2003). Positive selection is thought to be mediated by relatively weak non-agonist peptides (Hogquist et al 1994;Santori et al 2002) indicating that amplification of TCR signals generated from such interactions may be especially important for positive selection. Consistent with this notion, positive selection was found to be markedly impaired in zdeficient mice reconstituted with transgenes encoding ITAM mutant z chains (Shores et al 1994;Ardouin et al 1999;Pitcher et al 2005b).…”

Section: Potential Functions For Itam-mediated Signal Amplification Dmentioning

confidence: 99%

ITAM-mediated Signaling by the T-Cell Antigen Receptor

Love¹,

Hayes²

2010

Cold Spring Harbor Perspectives in Biology

164

148

View full text Add to dashboard Cite

“…However, none of these studies provides evidence that the respective peptides actually contribute to negative selection under physiological conditions. In the early nineties, Marrack et al 17 successfully identified B20 MHC IIbound peptides in pooled thymi of several hundred mice and a few natural ligands for positive selection of mouse OT-I cells are known 18,19 . More recently, another group has eluted peptides from whole-mouse thymus, using bioinformatics to narrow down on likely MHC I ligands 20 .…”

mentioning

confidence: 99%

Exploring the MHC-peptide matrix of central tolerance in the human thymus

et al. 2013

View full text Add to dashboard Cite

Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant crosstalk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune-and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.

show abstract

Rare, Structurally Homologous Self-Peptides Promote Thymocyte Positive Selection

Cited by 87 publications

References 54 publications

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

Investigation of Peptide Involvement in T Cell Allorecognition Using Recombinant HLA Class I Multimers

ITAM-mediated Signaling by the T-Cell Antigen Receptor

Exploring the MHC-peptide matrix of central tolerance in the human thymus

Contact Info

Product

Resources

About