Low-affinity peptides and T-cell selection

HLA class I-associated diseases with a suspected autoimmune etiology: HLA-B27 subtypes as a model system

“…These are the first results that reveal a correlation between dynamic properties of MHC molecules and a disease. Finally, we were able to shed new light on the process of T cell selection within the thymus ( [Rehm et al, 2000] and [Ziegler et al, 2009a]). …”

“…1C) (Hülsmeyer et al, 2002). This results in a pronounced destabilisation of the peptide C-terminus in the B*27:09 subtype, as shown by circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC) (Hillig et al, 2004) as well as by time-resolved fluorescence depolarisation spectroscopic measurements ( [Pöhlmann et al, 2004] and ), kinetic studies (Winkler et al, 2007), and molecular dynamics simulations ( [Pöhlmann et al, 2004] and [Ziegler et al, 2009a]). However, the m9 peptide remains firmly bound to the B*27:05 subtype.…”

“…In the B*27:09 subtype, however, the salt bridge-mediated contact between the m9 peptide and Asp77 is geometrically unfavourable and does not lead to a firm anchoring of m9 within this subtype's binding groove (Fig. 5B) ( [Hülsmeyer et al, 2002], [Pöhlmann et al, 2004], [Winkler et al, 2007], [Narzi et al, 2008] and [Ziegler et al, 2009a]). Peptide binding characteristics can be assessed particularly well when the interactive 3D mode is activated by clicking on the figure.…”

“…Peptide binding characteristics can be assessed particularly well when the interactive 3D mode is activated by clicking on the figure. The procedure to embed multimedia content (apart from molecular models and structures of zoological specimens, also videos, and audios) into electronic publications has been pioneered by us ( [Kumar et al, 2008], [Kumar et al, 2009a], [Kumar et al, 2009b], [Kumar et al, 2010], , [Ziegler et al, 2009a], [Ziegler et al, 2010b], [Ziegler et al, 2010c], , [Hee et al, 2010] and [Loll et al, 2011]). This development has been welcomed by structural biologists ( [Tyzack, 2008], [Hodis andSussman, 2009] and[Anon., 2009]).…”

On the issue of peptide recognition in T cell development

“…Others have suggested that MHC1 molecules loaded with low-binding affinity peptides, like those generated by cTECs, imply that two types of MHC ligands which have not been traditionally regarded as ligands for positive selection are likely to be presented on cTECs. 32 These namely include MHC-peptide complexes in which only one side of the peptide is anchored or empty MHC molecules from which peptides have completely disassociated. Antibodies that recognize MHC molecules in a peptide-dependent and independent manner have provided supporting evidence for the presence of such complexes on cortical cells but not within the medulla.…”