Dataset Information

The peptide repertoire of HLA-B27 includes ligands with lysine at P2 anchor position

ABSTRACT: The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS). The role of HLA-B*27 in this condition is not known yet. This study aims to expand the known limits of the HLA-B*27 peptidome in order to facilitate selection and testing of new peptides, possibly implicated with the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associated HLA-B*27:05 allele, the non-associated HLA-B*27:09 allele, or their mutants with Cysteine 67 replaced by Serine (C67S), were analyzed on a very large scale. In addition, the peptidomes of HLA-B*27:05 and HLA-B*27:05-C67S were analyzed from transgenic rats’ spleens. The results indicate that a fraction of HLA-B*27 peptides contain lysine at their second position (P2), in addition to the more commonly found peptides with arginine, or the less common glutamine located at this anchor position. Furthermore, the C67S mutation increases the percentages of peptides with glutamine or lysine at their P2 position, in both HLA-B*27:05 and HLA-B*27:09. Therefore, peptides with P2 lysine should be considered as valid ligands of HLA-B*27 molecules and taken into account while looking for candidate for arithrogenic peptides.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat) Homo Sapiens (human)

TISSUE(S): Spleen, Permanent Cell Line Cell

DISEASE(S): Ankylosis

SUBMITTER: Dganit Melamed Kadosh

LAB HEAD: Arie Admon

PROVIDER: PXD007756 | Pride | 2018-04-10

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 90

Publications

The Peptide Repertoire of HLA-B27 may include Ligands with Lysine at P2 Anchor Position.

Yair-Sabag Shira S Tedeschi Valentina V Vitulano Carolina C Barnea Eilon E Glaser Fabian F Melamed Kadosh Dganit D Taurog Joel D JD Fiorillo Maria Teresa MT Sorrentino Rosa R Admon Arie A

Proteomics 20180313 9

The HLA-B*27 peptidome has drawn significant attention due to the genetic association between some of the HLA-B*27 alleles and the inflammatory rheumatic disease ankylosing spondylitis (AS), for which a comprehensive biological explanation is still lacking. This study aims to expand the known limits of the HLA-B*27 peptidome to facilitate selection and testing of new peptides, possibly involved in the disease. The HLA peptidomes of HeLa and C1R cell lines stably transfected with the AS-associate ...[more]

PMID: 29393594

Similar Datasets

Project description:Human leukocyte antigen (HLA) - B*51:01 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are two strong predisposing genetic factors to Behçet's disease (BD). Previous studies have focused on two subgroups of HLA-B*51 peptidome containing Proline (Pro) or Alanine (Ala) at position 2 (P2). Little is known about the unconventional non-Pro/Ala2 HLA-B*51-bound peptides. We aimed to study the features of this novel sub-peptidome, and investigate its regulation by ERAP1. CRISPR-Cas9 was used to generate an HLA-ABC-knockout HeLa cell line (HeLa.ABC-KO), which was subsequently transduced to express HLA-B*51:01 (HeLa.ABC-KO.B51). ERAP1 was silenced using lentiviral shRNA. Peptides bound to HLA-B*51:01 were eluted and analyzed by Mass Spectrometry. The characteristics of non-Pro/Ala2, Pro2 and Ala2 peptides, and their alteration by ERAP1 silencing were investigated. Effects of ERAP1 silencing on cell surface expression of HLA-B*51:01 were studied using flow cytometry. More than 20% of peptides eluted from HLA-B*51:01 lacked Proline or Alanine at P2. This unconventional group of HLA-B*51:01-bound peptides was enriched for 8-mers (with fewer 9-mers) compared to Pro2 and Ala2 sub-peptidomes, and had similar N-terminal and C-terminal residue usages to Ala2 peptides with the exception of the less abundant Leucine at position Ω. Knockdown of ERAP1 increased the percentage of non-Pro/Ala2 to approximately 40%, increased the percentage of longer (10-mer and 11-mer) peptides eluted from HLA-B*51:01 complexes, and abrogated the predominance of Leucine at P1. Interestingly knockdown of ERAP1 altered the length and N-terminal residue usage of non-Ala2&Pro2 and Ala2 but not the Pro2 peptides. Finally, ERAP1 silencing regulated the expression levels of cell surface HLA-B*51 in a cell type - dependent manner. The HLA-B*51:01 peptidome includes a surprisingly high proportion of unconventional non-Pro/Ala2 peptides which are increased by ERAP1 silencing, mimicking the loss-of-function BD risk variant.

			Action	DRS
	51014-51026.rar	Other
	52202-05.rar	Other
	Seq35432_QE.raw	Raw
	Seq35433_QE.raw	Raw
	Seq35434_QE.raw	Raw