Related Experiment Video

Updated: Aug 10, 2026

Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
09:53

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

CD8alphabeta has two distinct binding modes of interaction with peptide-major histocompatibility complex class I

Hsiu-Ching Chang1, Kemin Tan, Yen-Ming Hsu

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. hsiu-ching_chang@dfci.harvard.edu

The Journal of Biological Chemistry
|July 15, 2006
PubMed

Insights

The CD8alphabeta co-receptor interacts with peptide-MHC class I (pMHCI) in multiple orientations. Specific CD8alpha and CD8beta variants reveal insights into CD8alphabeta heterodimer binding to pMHCI.

Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • CD8 co-receptor binding to peptide-MHC class I (pMHCI) is crucial for T cell immunity.
  • While CD8alphaalpha homodimer interaction with pMHCI is structurally characterized, the CD8alphabeta heterodimer's binding remains less understood.

Purpose of the Study:

  • To elucidate the interaction mechanism of the CD8alphabeta heterodimer with pMHCI.
  • To investigate the roles of individual CD8alpha and CD8beta subunits in pMHCI binding.

Main Methods:

  • Utilized site-directed mutagenesis to create CD8alpha and CD8beta variants.
  • Assessed co-receptor activity of engineered CD8alphabeta heterodimers in functional assays.
  • Investigated antibody blocking effects on CD8alphabeta-pMHCI interaction.

Main Results:

  • Functionally inactive CD8alpha homodimer variants formed active heterodimers with wild-type CD8beta.
  • Specific CD8beta variants could pair with wild-type CD8alpha but not with CD8alpha variants.
  • Anti-CD8alpha and anti-CD8beta antibodies did not fully inhibit CD8alphabeta co-receptor activity.

Conclusions:

  • The CD8beta subunit can substitute for a CD8alpha subunit in the CD8alphaalpha.pMHCI complex.
  • CD8alphabeta binds to pMHCI in at least two distinct orientations.
  • This study provides novel insights into the structural and functional diversity of CD8-pMHCI interactions.

More Related Videos

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin11:17

Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin

Published on: March 10, 2021

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis09:32

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

Published on: October 15, 2021

Related Concept Videos

Peptide Bonds02:43

Peptide Bonds

A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
83.2K
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.8K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
15.1K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
What is a Mode?01:07

What is a Mode?

The mode is one of the commonly used measures of a central tendency. It is defined as the most frequent value in a data set.
There can be more than one mode in a data set if multiple values have the same highest frequency. For instance, suppose that the Statistics exam scores of 20 students are: 50; 53; 59; 59; 63; 63; 72; 72; 72; 72; 72; 76; 78; 81; 83; 84; 84; 84; 90; 93. Here, the mode is 72, as it occurs most frequently, five times.
A data set with two modes is called bimodal. For example,...
26.3K
Factors Affecting Protein-Drug Binding: Drug Interactions01:23

Factors Affecting Protein-Drug Binding: Drug Interactions

Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
605