The biogenesis of the immunopeptidome

Admon, Arie

doi:10.1016/j.smim.2023.101766

“…Due to the rapid progress of MS and its related field, cancer immunotherapy, there remain countless significant publications and more details unmentioned in this review. Essential knowledge about immunopeptidomics has been described by an enormous number of publications, which were recently excellently summarized in the literature review of Admon et al 82 …”

Section: Discussionmentioning

confidence: 99%

Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy

Minegishi,

Haga,

Ueda

2024

Cancer Science

1

0

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With significant advances in analytical technologies, research in the field of cancer immunotherapy, such as adoptive T cell therapy, cancer vaccine, and immune checkpoint blockade (ICB), is currently gaining tremendous momentum. Since the efficacy of cancer immunotherapy is recognized only by a minority of patients, more potent tumor‐specific antigens (TSAs, also known as neoantigens) and predictive markers for treatment response are of great interest. In cancer immunity, immunopeptides, presented by human leukocyte antigen (HLA) class I, play a role as initiating mediators of immunogenicity. The latest advancement in the interdisciplinary multiomics approach has rapidly enlightened us about the identity of the “dark matter” of cancer and the associated immunopeptides. In this field, mass spectrometry (MS) is a viable option to select because of the naturally processed and actually presented TSA candidates in order to grasp the whole picture of the immunopeptidome. In the past few years the search space has been enlarged by the multiomics approach, the sensitivity of mass spectrometers has been improved, and deep/machine‐learning‐supported peptide search algorithms have taken immunopeptidomics to the next level. In this review, along with the introduction of key technical advancements in immunopeptidomics, the potential and further directions of immunopeptidomics will be reviewed from the perspective of cancer immunotherapy.

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“…Inferences on the immunopeptidome of thymic stromal cells are based on transcriptomic data. However, (i) TCRs interact with MAPs, not transcripts, and (ii) the MAP repertoire cannot be inferred from the transcriptome ( Shapiro and Bassani-Sternberg, 2023 ; Caron et al, 2011 ; Admon, 2023 ). Using K5D1 mice presenting prominent thymic hyperplasia, we conducted MS searches of TE MAPs, identifying four TE MAPs in mTECs and two in cTECs.…”

Section: Discussionmentioning

confidence: 99%

Transposable elements regulate thymus development and function

Larouche,

Laumont,

Trofimov

et al. 2024

eLife

4

0

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Transposable elements (TE) are repetitive sequences representing ∼45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTEC). In this study, we investigated the role of transposable elements (TE), which are highly expressed by medullary thymic epithelial cells (mTEC), on T-cell development in the thymus. We performed multi-omic analyses of TEs in human and mouse thymic cells to elucidate their role in T cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TEs interact with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDC). In mTECs, TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and RELB) and generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that lead to the formation of dsRNA, triggering RIG-I and MDA5 signaling and explaining why thymic pDCs constitutively secrete IFN ɑ/β. This study illustrates the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that the orchestration of TE expression in thymic cells is critical to prevent autoimmunity in vertebrates.

show abstract

“…Inferences on the immunopeptidome of thymic stromal cells are based on transcriptomic data. However, i) TCRs interact with MAPs, not transcripts, and ii) the MAP repertoire cannot be inferred from the transcriptome (65,83,84). Using K5D1 mice presenting prominent thymic hyperplasia, we conducted MS searches of TE MAPs, identifying 4 TE MAPs in mTECs and 2 in cTECs.…”

Section: Discussionmentioning

confidence: 99%

Transposable elements regulate thymus development and function

Laumont

¹

,

Trofimov

²

,

Vincent

³

et al. 2023

Preprint

1

0

View full text Add to dashboard Cite

Transposable elements (TE) are repetitive sequences representing ∼45% of the human and mouse genomes and are highly expressed by medullary thymic epithelial cells (mTEC). In this study, we investigated the role of transposable elements (TE), which are highly expressed by medullary thymic epithelial cells (mTEC), on T-cell development in the thymus. We performed multi-omic analyses of TEs in human and mouse thymic cells to elucidate their role in T cell development. We report that TE expression in the human thymus is high and shows extensive age- and cell lineage-related variations. TEs interact with multiple transcription factors in all cell types of the human thymus. Two cell types express particularly broad TE repertoires: mTECs and plasmacytoid dendritic cells (pDC). In mTECs, TEs interact with transcription factors essential for mTEC development and function (e.g., PAX1 and RELB) and generate MHC-I-associated peptides implicated in thymocyte education. Notably, AIRE, FEZF2, and CHD4 regulate non-redundant sets of TEs in murine mTECs. Human thymic pDCs homogenously express large numbers of TEs that lead to the formation of dsRNA, triggering RIG-I and MDA5 signaling and explaining why thymic pDCs constitutively secrete IFN ɑ/β. This study illustrates the diversity of interactions between TEs and the adaptive immune system. TEs are genetic parasites, and the two thymic cell types most affected by TEs (mTEcs and pDCs) are essential to establishing central T-cell tolerance. Therefore, we propose that the orchestration of TE expression in thymic cells is critical to prevent autoimmunity in vertebrates.

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The biogenesis of the immunopeptidome

Cited by 14 publications

References 420 publications

Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy

Emerging potential of immunopeptidomics by mass spectrometry in cancer immunotherapy

Transposable elements regulate thymus development and function

Transposable elements regulate thymus development and function

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