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TCR Gene Editing: Mechanisms, Enzymes, and Immunological Implications"

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This document provides a comprehensive overview of TCR (T-cell receptor) gene editing, focusing on its structure, function, and molecular mechanisms. It covers the historical background of TCR discovery, the structural composition of TCR and its association with the CD3 complex, and the genetic basis of TCR diversity through V(D)J recombination. The document explains the step-by-step process of V(D)J recombination, highlighting key enzymes such as RAG1, RAG2, Artemis, Ku70/Ku80, TdT, and LIG4, and their roles in DNA repair and recombination. Additionally, it discusses the implications of enzyme deficiencies, which can lead to immunodeficiencies and other health conditions. The document concludes with references to relevant literature in immunology and molecular biology.

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Voorbeeld van de inhoud

TCR gene editing

,Historical background




1976 1982 1984
Suzumi Tonegawa elucidates James P. Ellison isolates a new Mark M. Davis and colleag
the mechanism of B- protein complex that would be sequence the cDNA of th
lymphocyte receptor gene characterized as the T-cell variable chains of the TCR
rearrangement, for which he receptor humans and mice
receives the 1987 Nobel Prize in
Physiology or Medicine

,T-cell receptor: structure
Варіабельні ланцюги


 T-cell receptor (TCR) is a protein complex
surface of T cells that is responsible for recog
processed antigens bound to HCG proteins
surface of antigen-presenting cells and is
element in T-cell activation.
 Structurally, it is an octameric complex
 The TCR consists of two different protein
(heterodimer). In humans, in 95% of T-cells, th
consists of alpha α- and β- chains, while in 5%
cells, the TCR consists of γ- and δ- chains.
 The TCR subunits are aggregated with the mem
polypeptide complex CD3. CD3 is formed by fou
of polypeptides - γ, δ, ε and ζ. The γ, δ and ε su
are encoded by closely linked genes and have a
structure. Sometimes, instead of the ζ cha
complex includes the η chain - a longer product
same gene, obtained by alternative splicing.


Константні імуноглобулінові домени

, Molecular constructor


 Structure of the variable region of the T-
cell receptor: both chains contain a
constant domain (C) to which are
attached the variable regions of
variability (V), diversity (D), and junction
(J).
 The α-chain lacks diversity regions.
 The gene encoding all possible variable
region sequences is about 620 kilobases
long, while the average length of the
receptor coding sequence is only 500
base pairs.
 Why is this the case? The answer lies in a
process called V(D)J recombination.

, Event map
СD247
(СD3- ζ) The genes encoding the T
elements are located
СD3γ different chromosomes. T
TRB CD3δ
CD3ε
variable chains (marked in re
TRG
are located on chromosomes
and 14, with an interesti
TRA
pattern: the placement of α
TRD
and γδ- is “mirror”. T
invariant elements of the C
complex (marked in green) a
encoded on chromosomes
and 11.



A large number of proteins are also involved in the
process, catalyzing the recombination process at different
stages. The locations are marked in yellow.

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2024/2025
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