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Targeting the MHC Ligandome by Use of TCR-Like Antibodies

Monoclonal antibodies (mAbs) are valuable as research reagents, in diagnosis and in therapy. Their high specificity, the ease in production, favorable biophysical properties and the opportunity to engineer different properties make mAbs a versatile class of biologics. mAbs targeting peptide–major hi...

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Autores principales: Høydahl, Lene Støkken, Frick, Rahel, Sandlie, Inger, Løset, Geir Åge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640717/
https://www.ncbi.nlm.nih.gov/pubmed/31544838
http://dx.doi.org/10.3390/antib8020032
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author Høydahl, Lene Støkken
Frick, Rahel
Sandlie, Inger
Løset, Geir Åge
author_facet Høydahl, Lene Støkken
Frick, Rahel
Sandlie, Inger
Løset, Geir Åge
author_sort Høydahl, Lene Støkken
collection PubMed
description Monoclonal antibodies (mAbs) are valuable as research reagents, in diagnosis and in therapy. Their high specificity, the ease in production, favorable biophysical properties and the opportunity to engineer different properties make mAbs a versatile class of biologics. mAbs targeting peptide–major histocompatibility molecule (pMHC) complexes are often referred to as “TCR-like” mAbs, as pMHC complexes are generally recognized by T-cell receptors (TCRs). Presentation of self- and non-self-derived peptide fragments on MHC molecules and subsequent activation of T cells dictate immune responses in health and disease. This includes responses to infectious agents or cancer but also aberrant responses against harmless self-peptides in autoimmune diseases. The ability of TCR-like mAbs to target specific peptides presented on MHC allows for their use to study peptide presentation or for diagnosis and therapy. This extends the scope of conventional mAbs, which are generally limited to cell-surface or soluble antigens. Herein, we review the strategies used to generate TCR-like mAbs and provide a structural comparison with the analogous TCR in pMHC binding. We further discuss their applications as research tools and therapeutic reagents in preclinical models as well as challenges and limitations associated with their use.
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spelling pubmed-66407172019-09-05 Targeting the MHC Ligandome by Use of TCR-Like Antibodies Høydahl, Lene Støkken Frick, Rahel Sandlie, Inger Løset, Geir Åge Antibodies (Basel) Review Monoclonal antibodies (mAbs) are valuable as research reagents, in diagnosis and in therapy. Their high specificity, the ease in production, favorable biophysical properties and the opportunity to engineer different properties make mAbs a versatile class of biologics. mAbs targeting peptide–major histocompatibility molecule (pMHC) complexes are often referred to as “TCR-like” mAbs, as pMHC complexes are generally recognized by T-cell receptors (TCRs). Presentation of self- and non-self-derived peptide fragments on MHC molecules and subsequent activation of T cells dictate immune responses in health and disease. This includes responses to infectious agents or cancer but also aberrant responses against harmless self-peptides in autoimmune diseases. The ability of TCR-like mAbs to target specific peptides presented on MHC allows for their use to study peptide presentation or for diagnosis and therapy. This extends the scope of conventional mAbs, which are generally limited to cell-surface or soluble antigens. Herein, we review the strategies used to generate TCR-like mAbs and provide a structural comparison with the analogous TCR in pMHC binding. We further discuss their applications as research tools and therapeutic reagents in preclinical models as well as challenges and limitations associated with their use. MDPI 2019-05-09 /pmc/articles/PMC6640717/ /pubmed/31544838 http://dx.doi.org/10.3390/antib8020032 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Høydahl, Lene Støkken
Frick, Rahel
Sandlie, Inger
Løset, Geir Åge
Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title_full Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title_fullStr Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title_full_unstemmed Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title_short Targeting the MHC Ligandome by Use of TCR-Like Antibodies
title_sort targeting the mhc ligandome by use of tcr-like antibodies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640717/
https://www.ncbi.nlm.nih.gov/pubmed/31544838
http://dx.doi.org/10.3390/antib8020032
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