Abstract
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.
Highlights
IntroductionHuman leucocyte antigen (HLA)-class II molecules are heterodimers consisting of an alpha and beta chain presenting
Human leucocyte antigen (HLA)-class II molecules are heterodimers consisting of an alpha and beta chain presentingElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.2006; Melief and van der Burg 2008; Swain et al 2012)
To analyse whether the action of these proteases/peptidases would be reflected in conservations of particular aa residues in the N- and C-terminal peptide-positions, the frequency of individual aa residues was determined on eight positions located on the N- and C-termini: the four residues at the Nterminal and the four C-terminal residues (CP2, CP1, CP1′ and CP2′) of the complete human leucocyte antigen (HLA)-DR ligandome (Fig. 2a)
Summary
Human leucocyte antigen (HLA)-class II molecules are heterodimers consisting of an alpha and beta chain presenting. CD4+ T cells can play a detrimental role in immunity. CD4+ T cells targeting allergens are instrumental for class-switching towards an IgE response (Wambre et al 2012). CD4+ T cells are important effector cells as they could cause tissue damage, can help the priming of autoreactive CD8+ T cell responses and can be involved in Immunogenetics (2019) 71:519–530 the production of autoantibodies (Jones et al 2006). The contribution to auto-immunity is reflected by the association with the HLA-class II locus to many different autoimmune diseases (Shiina et al 2004). The HLA-system and CD4+ T cells play an important role in allograft rejection (Ali et al 2013)
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