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Related Concept Videos

Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
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Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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
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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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T Cell Activation and Clonal Selection

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Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.

Dan Feng1, Christopher J Bond, Lauren K Ely

  • 1Howard Hughes Medical Institute, Department of Molecular & Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.

Nature Immunology
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Summary

T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions exhibit a conserved binding pattern. Researchers identified specific interaction motifs between TCR V(beta) loops and MHC class II molecules, suggesting a

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Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Interactions

Background:

  • T cell receptors (TCRs) bind peptide-major histocompatibility complex (pMHC) molecules with a consistent binding polarity, despite diverse docking angles.
  • Previous TCR-pMHC crystal structures have not revealed broadly conserved interaction motifs.
  • Understanding these interactions is crucial for T cell recognition and immune response.

Purpose of the Study:

  • To investigate conserved interaction motifs between TCRs and MHC class II molecules.
  • To elucidate the structural basis of TCR-pMHC binding specificity.
  • To identify potential germline-derived interaction 'codons' in TCR-MHC recognition.

Main Methods:

  • Determined crystal structures of two T cell receptors (TCRs) encoded by variable beta-chain 8.2 (V(beta)8.2) bound to MHC class II molecule I-A(u).
  • Performed energetic mapping of V(alpha) and V(beta) chain contacts with I-A(u).
  • Analyzed four TCR-I-A complexes, including previously solved structures, for conserved interactions.

Main Results:

  • Identified structurally superimposable interactions between the V(beta) loops of four TCRs and the I-A alpha-helix.
  • Revealed conserved pairwise interaction motifs within a specific subset of the TCR-MHC repertoire.
  • Demonstrated a conserved binding pattern, or 'codon', for TCR-MHC interactions.

Conclusions:

  • The study identified conserved structural motifs in TCR-MHC interactions, specifically involving V(beta) loops and the I-A alpha-helix.
  • These findings suggest the existence of germline-derived interaction 'codons' that contribute to TCR-pMHC recognition.
  • This work provides insights into the molecular basis of T cell antigen recognition and immune response specificity.