Selection of multiple agonist antibodies from intracellular combinatorial libraries reveals that cellular receptors
Kyungmoo Yea1, Jia Xie2, Hongkai Zhang2
1Shanghai Institute for Advanced Immunological Studies, ShanghaiTech University, Shanghai 200031, China.
Abstract:
The main purpose of this perspective is to build on the unexpected outcomes of previous laboratory experiments using antibody agonists to raise questions concerning how activation of a given receptor can be involved in inducing differentiation of cells along different pathways some of which may even derive from different lineages. While not yet answered, the question illustrates how the advent of agonists not present in nature may give a different dimension to the important problem of signal transduction. Thus, if one studies a natural agonist-receptor system one can learn details about its signal transduction pathway. However, if one has a set of orthogonal agonists, one may learn about the yet undiscovered potential of the system that, in the end, may necessitate refinements to the currently used models. Thus, we wonder why receptors conventionally linked to a given pathway induce a different pattern of differentiation when agonized in another way.
Insights
Unexpected outcomes from laboratory experiments reveal that receptor activation can induce cell differentiation along diverse pathways. This challenges current models, suggesting novel signaling potentials beyond natural agonists.
Area of Science:
- Cellular biology
- Molecular signaling
- Immunology
Background:
- Antibody agonists have yielded unexpected experimental results.
- Understanding receptor-mediated cell differentiation is crucial.
Purpose of the Study:
- To explore how receptor activation by non-natural agonists influences cell differentiation pathways.
- To question the conventional understanding of receptor signaling and cell lineage determination.
Main Methods:
- Utilizing antibody agonists in laboratory experiments.
- Analyzing cell differentiation patterns induced by novel receptor activation.
Main Results:
- Receptor activation by antibody agonists can lead to differentiation along unexpected pathways.
- Observed differentiation patterns may involve cells from different lineages.
Conclusions:
- Non-natural agonists reveal undiscovered potentials of receptor systems.
- Current signal transduction models may require refinement based on these findings.
Related Concept Videos
Spare Receptors
Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Drug-Receptor Interactions
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....
Cross-reactivity
Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous...
Antibody Actions
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...


