Related Experiment Video

Updated: Dec 18, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

9.9K

Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen

Daichao Wu1,2,3, D Travis Gallagher1,4, Ragul Gowthaman1,3

  • 1W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.

Nature Communications
|June 11, 2020
PubMed

Insights

Researchers studied T-cell receptors (TCRs) targeting a shared cancer neoantigen from a p53 mutation. Structural analysis reveals how TCRs distinguish mutant from normal p53, aiding adoptive cell therapy (ACT) development.

Area of Science:

  • Immunology
  • Structural Biology
  • Oncology

Background:

  • Adoptive cell therapy (ACT) utilizes tumor-specific T cells for cancer regression.
  • Neoantigens, derived from mutated self-proteins, are key targets for T cells in ACT.
  • Shared neoantigens offer broader therapeutic potential than patient-unique ones.

Purpose of the Study:

  • To investigate T-cell receptors (TCRs) recognizing a shared neoepitope from the p53R175H mutation presented by HLA-A2.
  • To elucidate the structural basis of TCR recognition for mutant p53 neoantigens.

Main Methods:

  • X-ray crystallography was used to determine the structures of wild-type and mutant p53-HLA-A2 ligands.
  • Structures of three tumor-specific TCRs in complex with the p53R175H-HLA-A2 ligand were determined.
  • Comparative structural analysis of TCR-p53R175H-HLA-A2 complexes.

Main Results:

  • The study reports the structures of p53-HLA-A2 complexes and TCR complexes.
  • Structural insights reveal how the p53R175H mutation makes a self-peptide visible to T cells.
  • Distinct TCR structural strategies were identified for discriminating between mutant and wild-type p53.

Conclusions:

  • The identified TCR-p53R175H-HLA-A2 complexes provide a structural framework for understanding T-cell recognition of a shared cancer neoantigen.
  • This structural understanding can guide the design of enhanced TCRs for more potent and specific adoptive cell therapy.

More Related Videos

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens09:53

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens

Published on: February 6, 2017

11.7K
Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus13:41

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus

Published on: March 8, 2012

12.8K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
14.3K
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.4K
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and...
1.2K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.6K