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Related Concept Videos

Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

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...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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.
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Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

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Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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
Complete antigens possess both immunogenicity and reactivity.

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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
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c-IAP1 and c-IAP2 redundancy differs between T and B cells.

Maria Letizia Giardino Torchia1, Dietrich B Conze, Jonathan D Ashwell

  • 1Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Plos One
|June 27, 2013
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Cellular Inhibitors of Apoptosis 1 and 2 (c-IAP1 and c-IAP2) regulate NF-κB. While both repress non-canonical NF-κB activation, their specific roles and redundancy differ across cell types, impacting immune responses.

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Published on: September 7, 2018

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Cellular Inhibitors of Apoptosis 1 and 2 (c-IAP1 and c-IAP2) are E3 ubiquitin ligases.
  • They degrade NF-κB Inducing Kinase (NIK), repressing non-canonical NF-κB pathway activation.
  • Mice with inactive c-IAP2 exhibit constitutive NF-κB activation, leading to B cell hyperplasia and T cell costimulation-independence.

Purpose of the Study:

  • To investigate the redundancy between c-IAP1 and c-IAP2 in regulating NF-κB.
  • To characterize the in vivo function of c-IAP1's E3 ligase activity.

Main Methods:

  • Generation of mice expressing an E3-inactive c-IAP1 mutant (c-IAP1(H582A)).
  • Phenotypic analysis of c-IAP1(H582A) mice.
  • siRNA-mediated knockdown of c-IAP2 in relevant cell types.
  • Analysis of NF-κB pathway activation markers (p100/p52 ratio) and T cell proliferation.

Main Results:

  • Mice with inactive c-IAP1 were phenotypically normal, with no constitutive NF-κB activation.
  • Knockdown of c-IAP2 in c-IAP1(H582A) mice revealed compensatory mechanisms.
  • c-IAP1(H582A) T cells showed altered NF-κB signaling and intermediate proliferation compared to controls.
  • Cell type-specific differences in c-IAP1 and c-IAP2 function were observed.

Conclusions:

  • c-IAP1 and c-IAP2 exhibit functional redundancy in repressing constitutive NF-κB activation.
  • The relative importance of c-IAP1 and c-IAP2 in NF-κB regulation is cell type-dependent.
  • These findings provide insights into the complex regulation of the non-canonical NF-κB pathway.