T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1

dc.contributor.author	Stepniak, D	en
dc.contributor.author	Vader, LW	en
dc.contributor.author	Kooy, Y	en
dc.contributor.author	Van Veelen, PA	en
dc.contributor.author	Moustakas, A	en
dc.contributor.author	Papandreou, NA	en
dc.contributor.author	Eliopoulos, E	en
dc.contributor.author	Drijfhout, JW	en
dc.contributor.author	Papadopoulos, GK	en
dc.contributor.author	Koning, F	en
dc.date.accessioned	2014-06-06T06:46:40Z
dc.date.available	2014-06-06T06:46:40Z
dc.date.issued	2005	en
dc.identifier.issn	00937711	en
dc.identifier.uri	http://dx.doi.org/10.1007/s00251-005-0780-8	en
dc.identifier.uri	http://62.217.125.90/xmlui/handle/123456789/3125
dc.subject	Celiac disease	en
dc.subject	Gluten epitope	en
dc.subject	HLA-DQ2	en
dc.subject.other	gliadin	en
dc.subject.other	gluten	en
dc.subject.other	glutenin	en
dc.subject.other	HLA DQ2 antigen	en
dc.subject.other	peptide derivative	en
dc.subject.other	polypeptide	en
dc.subject.other	proline	en
dc.subject.other	T lymphocyte receptor	en
dc.subject.other	amino acid substitution	en
dc.subject.other	amino terminal sequence	en
dc.subject.other	antigen recognition	en
dc.subject.other	antigen specificity	en
dc.subject.other	article	en
dc.subject.other	controlled study	en
dc.subject.other	human	en
dc.subject.other	human cell	en
dc.subject.other	lymphocyte clone	en
dc.subject.other	molecular model	en
dc.subject.other	molecular weight	en
dc.subject.other	priority journal	en
dc.subject.other	protein binding	en
dc.subject.other	Amino Acid Sequence	en
dc.subject.other	Computer Simulation	en
dc.subject.other	Databases, Protein	en
dc.subject.other	Epitopes, T-Lymphocyte	en
dc.subject.other	Gluten	en
dc.subject.other	HLA-DQ Antigens	en
dc.subject.other	Humans	en
dc.subject.other	Lymphocyte Activation	en
dc.subject.other	Molecular Sequence Data	en
dc.subject.other	Peptide Fragments	en
dc.subject.other	Proline	en
dc.subject.other	T-Lymphocytes	en
dc.title	T-cell recognition of HLA-DQ2-bound gluten peptides can be influenced by an N-terminal proline at p-1	en
heal.type	journalArticle	en
heal.identifier.primary	10.1007/s00251-005-0780-8	en
heal.publicationDate	2005	en
heal.abstract	Recent research has implicated a large number of gluten-derived peptides in the pathogenesis of celiac disease, a preponderantly HLA-DQ2-associated disorder. Current evidence indicates that the core of some of those peptides is ten amino acids long, while HLA class II normally accommodates nine amino acids in the binding groove. We have now investigated this in detail, using gluten-specific T-cell clones, HLA-DQ2-specific peptide-binding assays and molecular modelling. T-cell recognition of both a γ-gliadin peptide and a low-molecular-weight glutenin peptide was found to be strictly dependent on a ten-amino acids-long peptide. Subsequent peptide-binding studies indicated that the glutenin peptide bound in a conventional p1/p9 register, with an additional proline at p-1. Testing of substitution analogues demonstrated that the nature of the amino acid at p-1 strongly influenced T-cell recognition of the peptide. Moreover, molecular modelling confirmed that the glutenin peptide binds in a p1/p9 register, and that the proline at p-1 points upward towards the T-cell receptor. Database searches indicate that a large number of potential T-cell stimulatory gluten peptides with an additional proline at relative position p-1 exist, suggesting that the recognition of other gluten peptides may depend on this proline as well. This knowledge may be of importance for the identification of additional T-cell stimulatory gluten peptides and the design of a peptide-based, tolerance-inducing therapy. © Springer-Verlag 2005.	en
heal.journalName	Immunogenetics	en
dc.identifier.issue	1-2	en
dc.identifier.volume	57	en
dc.identifier.doi	10.1007/s00251-005-0780-8	en
dc.identifier.spage	8	en
dc.identifier.epage	15	en