All T cells express cell‑surface antigen receptors (TCRs), which are encoded by genes that are assembled from multiple gene segments during T cell development in the thymus. TCRs recognize peptide fragments of foreign proteins that are displayed in association with MHC proteins on the surface of antigen‑presenting cells (APCs) and target cells. Naïve T cells are activated in peripheral lymphoid organs by activated dendritic cells, which secrete cytokines and express peptide–MHC complexes, co‑stimulatory proteins, and various cell–cell adhesion molecules on their cell surface.
Class I MHC proteins present foreign peptides to TC cells, whereas class II MHC proteins present foreign peptides to TH cells and Treg cells. Whereas class I MHC proteins are expressed on almost all nucleated vertebrate cells, class II MHC proteins are normally restricted to APCs, including dendritic cells, macrophages, and B lymphocytes. Both classes of MHC proteins have a single peptide‑binding groove, which binds a large set of small peptide fragments produced intracellularly by normal protein‑degradation processes: class I MHC proteins mainly bind fragments produced in the cytosol, whereas class II MHC proteins mainly bind fragments produced in endocytic compartments. The peptide–MHC complexes are transported to the cell surface, where complexes that contain a peptide derived from a foreign protein are recognized by TCRs, which interact with both the peptide and the walls of the peptide‑binding groove. T cells also express CD4 or CD8 co‑receptors, which recognize invariant regions of MHC proteins: TH cells and Treg cells express CD4, which recognizes class II MHC proteins; TC cells express CD8, which recognizes class I MHC proteins.
A combination of positive and negative selection operates during T cell development in the thymus to help ensure that only T cells with potentially useful TCRs survive, mature, and emigrate, while all of the others die by apoptosis. The naïve TH and TC cells that leave the thymus constantly receive survival signals when their TCRs recognize self‑peptide–MHC complexes, but they can only be activated when their TCRs encounter foreign peptides in the grooves of MHC proteins on an activated dendritic cell. The natural Treg cells that leave the thymus suppress self‑reactive lymphocytes to help maintain self‑tolerance.
The production of an effector T cell from a naïve T cell requires multiple signals from an activated dendritic cell. MHC–peptide complexes on the dendritic cell surface provide one signal, by binding to both TCRs and a CD4 co‑receptor on a TH or Treg cell. Co‑stimulatory proteins on the dendritic cell surface and secreted cytokines are the other signals. When naïve TH cells are initially activated on a dendritic cell, they differentiate into TH1, TH2, TFH, or TH17 effector helper cells or into induced Treg cells, depending mainly on the cytokines in their environment. TH1 cells secrete interferon‑γ (IFNγ) to activate macrophages and to induce B cells to switch the class of Ig they make; TH2 and TFH cells secrete other cytokines that also induce B cells to switch Ig class; and TH17 cells secrete IL17 to promote inflammatory responses
What initiates an autoimmune disease such as type 1 diabetes or multiple sclerosis?
When a naïve or memory T or B cell is activated by antigen and co-stimulatory signals, how does it decide whether to become an effector cell or memory cell? Are there cells that are pre-committed to becoming either effector or memory cells, for example, or is the decision determined solely by extracellular signals?
Why do some of us make Ige antibodies against harmless antigens and thereby develop hay fever and allergic asthma, while most of us do not, and why is the proportion of such allergic individuals increasing?