Research Topic

Decoding Immune Synapses to Enable Next Generation Immunotherapies

About this Research Topic

As a key component of the adaptive immune system, T cells are major mediators of autoimmune diseases, but also protect us from cancer and infections. They do so by recognizing peptides derived from specific disease-relevant antigens through their T cell receptor (TCR). These peptides are bound to human leukocyte antigen (HLA) proteins on the surface of specialized antigen presenting cells or body cells. A TCR recognizes one or a few specific peptide-HLA (pHLA) complexes in a manner that is restricted by a person's HLA haplotype. TCR-binding to a pHLA complex results in the formation of an "immune synapse" which then triggers T cell proliferation and effector processes such as cytokine production and killing of bound cells. Impaired T cell homeostasis or function is increasingly recognized as a major contributor to many if not most human diseases. Not surprisingly, many therapies target T cells. But insufficient knowledge of disease-relevant antigens and of the specific T cell clonotypes recognizing them has limited most therapeutic approaches to non-specific T cell inhibition for autoimmune diseases, or to non-specific activation for infectious diseases or cancer. Although it promises unparalleled safety and efficacy, clonotype-specific intervention has remained the "Holy Grail" of immunology. Novel technology now promises to usher in the next generation of clonotype-specific immunotherapies.

Despite some remarkable progress in disease control, current immune therapies for cancer, autoimmune and infectious diseases are limited by insufficient specificity for disease-critical antigens. As a consequence, efficacy is restricted by antigen paucity or mutation for example in cancers, or by an inability to selectively and permanently inactivate or deplete disease-promoting T cells in autoimmune disorders. Conversely, current treatments have sometimes severe toxicities in part reflecting cross-reactivities or broad immune activation or suppression. To overcome these limitations, more selective and specific immune medicines are urgently needed. The articles in this Research Topic will highlight and critically review recent technological advances in decoding immune synapses. Particular attention is given to how this enables clonotype-specific next generation immunotherapies that promise transformative gains in both efficacy and safety.

This Research Topic solicits Original Research and Review articles exploring novel technologies to decode immune synapses and their application to develop next-generation, synapse-targeted immunotherapies. Topics of interest include, but are not limited to, the following:

• Single-cell sequencing based and reporter cell based decoding of antigen epitopes, pHLA complexes, matched T cell clonotypes and their phenotypes
• Peptide elution/mass spectrometry-based epitope identification
• Computational prediction of antigen epitopes
• Computational prediction of antigen-specific T cell clonotypes
• Decoding non-canonical antigens and post-translational modifications
• Decoding B cells
• Decoding genetic interdependencies of HLA haplotype and T cell responses
• Antigen-specific therapeutics: T cells, pHLA-targeted immunomodulators
• Clonotype-specific therapeutics: Cells, TCR-targeted immunomodulators
• Treg cell therapies - how important is antigen selectivity?
• Using decoded immune synapses as diagnostics and clinical biomarkers

Dr. Karsten Sauer and Dr. Tim Harris are employees of Repertoire Immune Medicines, related to the understanding of the immune synapse and the development of immunomodulators in T Cells


Keywords: T cell, B cell, repertoire, epitope, antigen, clonotype, single cell sequencing, TCR, vaccine, HLA, MHC, Treg cell, immune synapse, cancer, autoimmune disease, infection, neurodegenerative disease, immunotherapy, biomarker, diagnostic


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

As a key component of the adaptive immune system, T cells are major mediators of autoimmune diseases, but also protect us from cancer and infections. They do so by recognizing peptides derived from specific disease-relevant antigens through their T cell receptor (TCR). These peptides are bound to human leukocyte antigen (HLA) proteins on the surface of specialized antigen presenting cells or body cells. A TCR recognizes one or a few specific peptide-HLA (pHLA) complexes in a manner that is restricted by a person's HLA haplotype. TCR-binding to a pHLA complex results in the formation of an "immune synapse" which then triggers T cell proliferation and effector processes such as cytokine production and killing of bound cells. Impaired T cell homeostasis or function is increasingly recognized as a major contributor to many if not most human diseases. Not surprisingly, many therapies target T cells. But insufficient knowledge of disease-relevant antigens and of the specific T cell clonotypes recognizing them has limited most therapeutic approaches to non-specific T cell inhibition for autoimmune diseases, or to non-specific activation for infectious diseases or cancer. Although it promises unparalleled safety and efficacy, clonotype-specific intervention has remained the "Holy Grail" of immunology. Novel technology now promises to usher in the next generation of clonotype-specific immunotherapies.

Despite some remarkable progress in disease control, current immune therapies for cancer, autoimmune and infectious diseases are limited by insufficient specificity for disease-critical antigens. As a consequence, efficacy is restricted by antigen paucity or mutation for example in cancers, or by an inability to selectively and permanently inactivate or deplete disease-promoting T cells in autoimmune disorders. Conversely, current treatments have sometimes severe toxicities in part reflecting cross-reactivities or broad immune activation or suppression. To overcome these limitations, more selective and specific immune medicines are urgently needed. The articles in this Research Topic will highlight and critically review recent technological advances in decoding immune synapses. Particular attention is given to how this enables clonotype-specific next generation immunotherapies that promise transformative gains in both efficacy and safety.

This Research Topic solicits Original Research and Review articles exploring novel technologies to decode immune synapses and their application to develop next-generation, synapse-targeted immunotherapies. Topics of interest include, but are not limited to, the following:

• Single-cell sequencing based and reporter cell based decoding of antigen epitopes, pHLA complexes, matched T cell clonotypes and their phenotypes
• Peptide elution/mass spectrometry-based epitope identification
• Computational prediction of antigen epitopes
• Computational prediction of antigen-specific T cell clonotypes
• Decoding non-canonical antigens and post-translational modifications
• Decoding B cells
• Decoding genetic interdependencies of HLA haplotype and T cell responses
• Antigen-specific therapeutics: T cells, pHLA-targeted immunomodulators
• Clonotype-specific therapeutics: Cells, TCR-targeted immunomodulators
• Treg cell therapies - how important is antigen selectivity?
• Using decoded immune synapses as diagnostics and clinical biomarkers

Dr. Karsten Sauer and Dr. Tim Harris are employees of Repertoire Immune Medicines, related to the understanding of the immune synapse and the development of immunomodulators in T Cells


Keywords: T cell, B cell, repertoire, epitope, antigen, clonotype, single cell sequencing, TCR, vaccine, HLA, MHC, Treg cell, immune synapse, cancer, autoimmune disease, infection, neurodegenerative disease, immunotherapy, biomarker, diagnostic


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 December 2021 Abstract
31 March 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 December 2021 Abstract
31 March 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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