Pathway: CTLA4 inhibitory signaling
Reactions in pathway: CTLA4 inhibitory signaling :
CTLA4 inhibitory signaling
CTLA4 is one of the best studied inhibitory receptors of the CD28 superfamily. CTLA4 inhibits T cell activation by reducing IL2 production and IL2 expression, and by arresting T cells at the G1 phase of the cell cycle. CTLA-4 expressed by a T cell subpopulation exerts a dominant control on the proliferation of other T cells, which limits autoreactivity. CTLA4 also blocks CD28 signals by competing for the ligands B71 and B72 in the limited space between T cells and antigenpresenting cells. Though the mechanism is obscure, CTLA4 may also propagate inhibitory signals that actively counter those produced by CD28. CTLA4 can also function in a ligand-independent manner.
CTLA-4 regulates the activation of pathogenic T cells by directly modulating T cell receptor signaling (i.e. TCR-zeta chain phosphorylation) as well as downstream biochemical signals (i.e. ERK activation). The cytoplasmic region of CTLA4 contains a tyrosine motif YVKM and a proline rich region. After TCR stimulation, it undergoes tyrosine phosphorylation by src kinases, inducing surface retention.
CTLA-4 regulates the activation of pathogenic T cells by directly modulating T cell receptor signaling (i.e. TCR-zeta chain phosphorylation) as well as downstream biochemical signals (i.e. ERK activation). The cytoplasmic region of CTLA4 contains a tyrosine motif YVKM and a proline rich region. After TCR stimulation, it undergoes tyrosine phosphorylation by src kinases, inducing surface retention.
Adaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with remarkable diversity tailored to recognize aspects of particular pathogens or antigens. During infection, dendritic cells (DC) which act as sentinels in the peripheral tissues recognize and pick up the pathogen in the form of antigenic determinants and then process these antigens and present them to T cells. These T cells of appropriate specificity respond to the antigen, and either kill the pathogen directly or secrete cytokines that will stimulate B lymphocyte response. B cells provide humoral immunity by secreting antibodies specific for the pathogen or antigen.
Humans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first critical hours and days of exposure to a new pathogen, our innate immune system.