Peptides presented by HLA class I molecules in the human thymus

Espinosa, Gabriel; Collado, Javier; Scholz, Erika; Mestre-Ferrer, Anna; Kuse, Nozomi; Takiguchi, Masafumi; Carrascal, Montserrat; Canals, Françesc; Pujol-Borrell, Ricardo; Jaraquemada, Dolores; Álvarez, Iñaki

doi:10.1016/j.jprot.2013.08.023

Cited by 14 publications

(10 citation statements)

References 52 publications

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“…The results by Adamopoulou et al essentially agree with our data, confirming a large number of source proteins of diverse origin and a clear “cross-talk” between the MHC-I and -MHC-II pathways of antigen processing. Recent results from our group on the MHC-I-associated thymus peptidoma (13) show similar results including the presentation of 20% peptides derived from proteins processed by the exogenous pathway. Thus, the “non-conventional” pathways of MHC-I and -II processing, i.e., cross-presentation of exogenous antigens by MHC-I and autophagy and uptake of apoptosis material for the presentation of cytosolic proteins by MHC-II, are efficiently acting in the thymus.…”

Section: Peptide Repertoire In Thymussupporting

confidence: 58%

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

et al. 2013

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T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions.

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Section: Peptide Repertoire In Thymussupporting

confidence: 58%

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

et al. 2013

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“…A total of 177 and 560 peptide ligands were identified from the DR2a and DR2b molecules, respectively. Peptides derived from some heterogeneous nuclear ribonucleoproteins were considered as background contaminants on the basis of their particular features (their sequences were notably rich in Gly and Pro) and of our previous observations [similar peptides had been found in previous analysis of other unrelated HLA-II and HLA-I molecules ( 32 )]. Thus, a final list of 169 unique peptides for DR2a and 555 unique peptides for DR2b were considered.…”

Section: Resultsmentioning

confidence: 99%

Human Leukocyte Antigen (HLA)-DRB115:01 and HLA-DRB501:01 Present Complementary Peptide Repertoires

et al. 2017

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Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear. In addition, the contribution of each molecule to the global peptide repertoire presented by the HLA-DR15 haplotype has not been evaluated.We used mass spectrometry to analyze the peptide pools bound to DR2a and DR2b, identifying 169 and 555 unique peptide ligands of DR2a and DR2b, respectively. The analysis of these sets of peptides allowed the refinement of the corresponding binding motifs revealing novel anchor residues that had been overlooked in previous analyses. Moreover, the number of shared ligands between both molecules was low, indicating that DR2a and DR2b present complementary peptide repertoires to T cells. Finally, our analysis suggests that, quantitatively, both molecules contribute to the peptide repertoire presented by cells expressing the HLA-DR15 haplotype.

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“…Peptides were analyzed using a 3-dimensional ion-trap mass spectrometer (Esquire HCT Ultra; Bruker Daltonics) (19,30) and a highresolution quadrupole/linear ion-trap mass spectrometer (LTQOrbitrap XL; Thermo Fisher) (30)(31)(32). Procedures are detailed in Supporting Information, http://onlinelibrary.wiley.com/doi/10.…”

Section: Methodsmentioning

confidence: 99%

A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis

Scholz

Mestre-Ferrer

Daura

et al. 2016

Arthritis & Rheumatology

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Objective To evaluate similarity of the peptide repertoires bound to HLA–DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides. Methods Peptide pools bound to HLA–DRB1*01:01, HLA–DRB1*04:01, and HLA–DRB1*10:01 (RA associated) and those bound to HLA–DRB1*15:01 (non–RA–associated) were purified and analyzed by liquid chromatography (LC) matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry (MS) and LC–ion‐trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA–DRB1 molecules and HLA–DRB5*01:01. Results A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions. Conclusion The degree of overlap between peptide repertoires associated with different HLA–DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu4 and basic residues at the P8 position of the binding core.

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Peptides presented by HLA class I molecules in the human thymus

Cited by 14 publications

References 52 publications

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

Human Leukocyte Antigen (HLA)-DRB115:01 and HLA-DRB501:01 Present Complementary Peptide Repertoires

A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis

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Peptides presented by HLA class I molecules in the human thymus

Cited by 14 publications

References 52 publications

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?

Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires

A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis

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Human Leukocyte Antigen (HLA)-DRB115:01 and HLA-DRB501:01 Present Complementary Peptide Repertoires