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Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft

Human CD4+ T lymphocytes play an important role in inducing potent immune responses. T cells are activated and stimulated by peptides presented in human leucocyte antigen (HLA)-class II molecules. These HLA-class II molecules typically present peptides of between 12 and 20 amino acids in length. The...

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Autores principales: Kampstra, Arieke S.B., van Heemst, Jurgen, Janssen, George M., de Ru, Arnoud H., van Lummel, Menno, van Veelen, Peter A., Toes, René E.M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790208/
https://www.ncbi.nlm.nih.gov/pubmed/31520135
http://dx.doi.org/10.1007/s00251-019-01129-6
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author Kampstra, Arieke S.B.
van Heemst, Jurgen
Janssen, George M.
de Ru, Arnoud H.
van Lummel, Menno
van Veelen, Peter A.
Toes, René E.M.
author_facet Kampstra, Arieke S.B.
van Heemst, Jurgen
Janssen, George M.
de Ru, Arnoud H.
van Lummel, Menno
van Veelen, Peter A.
Toes, René E.M.
author_sort Kampstra, Arieke S.B.
collection PubMed
description Human CD4+ T lymphocytes play an important role in inducing potent immune responses. T cells are activated and stimulated by peptides presented in human leucocyte antigen (HLA)-class II molecules. These HLA-class II molecules typically present peptides of between 12 and 20 amino acids in length. The region that interacts with the HLA molecule, designated as the peptide-binding core, is highly conserved in the residues which anchor the peptide to the molecule. In addition, as these peptides are the product of proteolytic cleavages, certain conserved residues may be expected at the N- and C-termini outside the binding core. To study whether similar conserved residues are present in different cell types, potentially harbouring different proteolytic enzymes, the ligandomes of HLA-DRB1*03:01/HLA-DRB > 1 derived from two different cell types (dendritic cells and EBV-transformed B cells) were identified with mass spectrometry and the binding core and N- and C-terminal residues of a total of 16,568 peptides were analysed using the frequencies of the amino acids in the human proteome. Similar binding motifs were found as well as comparable conservations in the N- and C-terminal residues. Furthermore, the terminal conservations of these ligandomes were compared to the N- and C-terminal conservations of the ligandome acquired from dendritic cells homozygous for HLA-DRB1*04:01. Again, comparable conservations were evident with only minor differences. Taken together, these data show that there are conservations in the terminal residues of peptides, presumably the result of the activity of proteases involved in antigen processing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-019-01129-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-67902082019-10-17 Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft Kampstra, Arieke S.B. van Heemst, Jurgen Janssen, George M. de Ru, Arnoud H. van Lummel, Menno van Veelen, Peter A. Toes, René E.M. Immunogenetics Original Article Human CD4+ T lymphocytes play an important role in inducing potent immune responses. T cells are activated and stimulated by peptides presented in human leucocyte antigen (HLA)-class II molecules. These HLA-class II molecules typically present peptides of between 12 and 20 amino acids in length. The region that interacts with the HLA molecule, designated as the peptide-binding core, is highly conserved in the residues which anchor the peptide to the molecule. In addition, as these peptides are the product of proteolytic cleavages, certain conserved residues may be expected at the N- and C-termini outside the binding core. To study whether similar conserved residues are present in different cell types, potentially harbouring different proteolytic enzymes, the ligandomes of HLA-DRB1*03:01/HLA-DRB > 1 derived from two different cell types (dendritic cells and EBV-transformed B cells) were identified with mass spectrometry and the binding core and N- and C-terminal residues of a total of 16,568 peptides were analysed using the frequencies of the amino acids in the human proteome. Similar binding motifs were found as well as comparable conservations in the N- and C-terminal residues. Furthermore, the terminal conservations of these ligandomes were compared to the N- and C-terminal conservations of the ligandome acquired from dendritic cells homozygous for HLA-DRB1*04:01. Again, comparable conservations were evident with only minor differences. Taken together, these data show that there are conservations in the terminal residues of peptides, presumably the result of the activity of proteases involved in antigen processing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-019-01129-6) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-09-13 2019 /pmc/articles/PMC6790208/ /pubmed/31520135 http://dx.doi.org/10.1007/s00251-019-01129-6 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Kampstra, Arieke S.B.
van Heemst, Jurgen
Janssen, George M.
de Ru, Arnoud H.
van Lummel, Menno
van Veelen, Peter A.
Toes, René E.M.
Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title_full Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title_fullStr Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title_full_unstemmed Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title_short Ligandomes obtained from different HLA-class II-molecules are homologous for N- and C-terminal residues outside the peptide-binding cleft
title_sort ligandomes obtained from different hla-class ii-molecules are homologous for n- and c-terminal residues outside the peptide-binding cleft
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790208/
https://www.ncbi.nlm.nih.gov/pubmed/31520135
http://dx.doi.org/10.1007/s00251-019-01129-6
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