T細胞受容体α多様性の起源と進化的可塑性

Orlando B Giorgetti¹, Connor P O'Meara², Michael Schorpp²

¹Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. orlandogiorgetti@gmail.com.

Nature

|June 21, 2023

まとめ

適応性免疫の進化には,DNA再結合部位におけるマイクロホモロジーの選択が含まれていた. この選択は早期の脊椎動物における自己認識のリスクと受容体の多様性を均衡させた.

科学分野:

免疫学
進化生物学
遺伝学

背景:

脊椎動物の適応免疫システムは,特定の病原体認識のために,抗体やT細胞受容体 (TCRs) などの体内で生成された抗原受容体を利用する.
多様な抗原受容体の生成は,遺伝子セグメントの組み立てを含むプロセスであるV(D) J再結合に依存する.
この受容体多様化メカニズムの進化的起源と自己認識とのバランスは,まだ完全に理解されていません.

研究の目的:

再結合要素の末端の配列マイクロホモロジーは,抗原受容体の多様性の進化軌跡に影響を与えたという仮説を調査する.
これらのマイクロホモロジーの選択が,自己反応性のリスクと拡張された受容体レパートリーの利点をどのようにバランスさせるかを探求する.

主な方法:

の脊椎動物群のV(D) J再結合要素の末端におけるシーケンスマイクロホモロジーの分析.
これらのマイクロホモロジーの範囲とTCRαレパートリーの多様性を相関させる.

主要な成果:

リコンビネーション要素におけるシーケンスマイクロホモロジーの種特有の範囲は,主要なの脊椎動物群のTCRαレパートリー多様性を有意に説明する.
証拠は,選択がこれらの元素の生殖序列の組成に作用したことを示唆している.

結論:

V(D) J再結合部位における配列マイクロホモロジーの選択は,体的に生成された抗原受容体の多様性を形成する重要な要因であった.
このメカニズムは,脊椎動物の初期の進化において,自己反応性の制御と免疫レパートリー拡大のバランスをとる上で重要な役割を果たした.

さらに関連する動画

08:59

T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing

Published on: January 12, 2021

8.3K

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

11.5K

関連する概念動画

01:28

Diversity of Antigen Receptors

659

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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...

659

01:22

T Cell Activation and Clonal Selection

837

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...

837

02:32

Exon Recombination

3.6K

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.
Exon shuffling follows “splice frame rules.” Each exon...

3.6K

01:23

Cells of the Adaptive Immune Response

1.1K

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...

1.1K

02:13

Overview of Transposition and Recombination

15.8K

Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...

15.8K

01:20

Mismatch Repair

4.9K

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.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...