T Cells: T-Cell Receptors and Functions
Terms in this set (17)
Membrane proteins that bind peptide fragments of intracellularly-degraded antigens, carry them to the cell surface, and present them to T-cells. Individual proteins of this kind can bind to families of related peptides. Different allelic forms of this protein binds to different peptides leading to the genetic variation in immune responsiveness.
Major Histocompatibility Gene Complex
A large multigene family found in all vertebrates that encodes the MHC proteins
This receptor recognizes peptide fragments of intracellularly degraded antigens presented by membrane MHC proteins on the surfaces of cells. It is a dimer with Ig variable and constant like regions. There exists 2 types of dimers, αβ and γδ. αβ are more expressed by the most common types of T cells, Th and Tc. They have have one binding site for the peptide, the MHC complex. The chains that make up this structure are encoded by separate families of V, D, J, and C gene segments that undergo DNA rearrangements during the maturation of T cells in the thymus.
MHC Class I
This class of MHC proteins bind peptides from cytoplasmic proteins, usually made by the cell, generated by cytosolic degredation (ex: peptides from viral or tumor antigens in infected or malignant cells.) It binds to antigen derived peptides in it antigen binding groove.
MHC Class II
This class of MHC proteins binds peptides derived from endocytosed foreign antigens, generated by degredation in endosome/lysosome.
TCR binding site
This part of the TCR is made up of 6 complementarity determining regions similar to the antigen binding site of antibodies. The CDRs in the middle bind to the antigen derived peptide and the ones on the outside bind to the MHC.
Cytotoxic T lymphocytes (Tc or CTL)
these cells kill cells containing foreign antigen that may be harmful to the body such as tumor cels and virus-infected cells.
Recognition of antigen peptides and MHC class I complex
First, the foreign antigen is chopped up by proteases in the cytoplasm. Then, the peptides go to the ER where peptides are recognized by MHC class I proteins and become bound to them. Next, the complex goes to the cell surface where it is recognized by the TCR. The CD8 membrane protein also binds the complex on the Tc.
activation phase of cytotoxic T-cells
When naïve T-cells recognize the MHC class I and peptide complex, via their TCR and CD8, they are activated to proliferate. Some of the daughter cells become killer T cells or CTL, and some daughter cells become memory cells.
Effector phase of cytotoxic T-cells
After CTL cells have matured, they circulate around the body and are recruited to the site of infection. When these CTLs recognize the same complex that activated them, they secrete perforin and other proteins which induce the target cell to undergo apoptosis.
helper T cells (Th)
The major function of this cell is to interact with B cells and provide signals from both cell-cell contact and cytokines secreted by Th that help activate B cells to give rise to both plasma cells secreting antibodies and memory cells.
Recognition of antigen peptides and MHC class II complex
The MHC Class II proteins travel through the endosome where they bind to chopped up peptides of foreign antigens that have been pre digested in the endosome.
Activation phase of helper T-cells
Unlike naïve cytotoxic T-cells, naïve helper T-cells are initially activated by secondary lymphoid tissues like macrophages and dendritic cells that have endocytosed the antigen. In the macrophage, the MHC class II protein binds to the peptides in the endosome. The TCR and CD4 on the helper T-cell recognize the MHC class II and peptide complex which activates helper T-cell proliferation into mature helper T cells and memory cells.
Effector phase of helper T-cells
When B-cells bind an antigen through their BCR, it triggers receptor mediated endocytosis and lysosomal/endosomal degredation. Here, like in the macrophages, the MHC class II proteins bind to the antigen peptides where this complex is take near the cell surface. Cell-cell contact with mature T cells make it secretes cytokines right onto the surface of the B-cell where the B-cell binds to the cytokines via its cytokine receptor which provides additional signals the B cell needs to become fully activated to divide and differentiate into antibody-secreting plasma cells and memory cells.
Functions of helper T-cells
Contribute in activating B-cells
Contribute in activating cytotoxic T-cells divide and differentiate into more CTL and memory cells
Activate macrophages to express more MHC class II proteins and be better antigen presenting cells
Others, called regulatory T-cells, Treg, inhibit T-cell activation
APC (antigen presenting cells)
These cells present antigen to T cells and help activate T-cells after which T-cells begin to proliferate.
preventing autoimmunity (immune cells reactive to self)
During development of B and T cells, regulatory processes cause most self reactive cells to die by apoptosis. Regulatory T cells also take care of eliminating or inactivating self reactive cells.