![]() The V H7183 and V HQ52 families-blue and red bars, respectively (lower panel)-are located at the D HJ H-proximal end of the locus. ( A) (Upper panel) Schematic diagram of the Igh locus showing the V Hs, Ds, J Hs, and C H exons and regulatory elements (not to scale). The Igh locus spans 2.9 Mb and contains about 100 V H gene segments. Double-strand DNA breaks are generated at RSSs by RAG1/2, and the V, D, and J exons are joined together through non-homologous end joining 4. Within each antigen receptor locus, the RAG recombinase concentrates in the recombination center (RC) that is focused to the J segment–containing domain. RAG1 contains endonuclease activity and targets the RSS, and RAG2 is recruited to the epigenetically modified histone 3 when it is trimethylated on lysine 4 3. During V(D)J recombination, two RSSs adjacent to V, D, or J gene segments partner such that cleavage and rejoining occur. This process depends on the lymphocyte-specific V(D)J recombinase, RAG1/2, which recognizes recombination signal sequences (RSSs) that flank all V, D, and J gene segments 3. V(D)J recombination is a stepwise process during which D H-to-J H recombination occurs first followed by V H-to-D HJ H rearrangement. Igh variable-region exons are produced by the joining of one each of the many variable (V), diversity (D), and joining (J) gene segments, whereas Igκ and Igλ are created by joining one each of the V and J gene segments, all by V(D)J recombination during lymphocyte development ( Figure 1B). The organization of the Igh and Igκ loci are schematically depicted ( Figure 1A and Figure 2A). Antigen receptors are composed of variable (V) and constant (C) regions. TCRαβ is encoded by the Tcra and Tcrb loci, whereas TCRγδ is encoded by the Tcrg and Tcrd loci. There are two lineages of T cells that are distinguished by the type of T-cell receptor (TCR) expressed. The B-cell receptor (BCR) is composed of two identical immunoglobulin (Ig) heavy chains (IgH) and two identical light chains (Igκ or Igλ). ![]() In vertebrates, the adaptive immune response is capable of recognizing pathogens using antigen-specific receptors expressed on B and T lymphocytes.
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