Induction of CMI
Antigen processing and presentation are the means by which antigens become associated with self-MHC molecules for pre-sentation to T cells with appropriate receptors. Proteins from exogenous antigens, such as bacteria, are internalized via endo-cytic vesicles into APCs, such as macrophages. Then, they are exposed to cellular proteases in intracellular vesicles. Peptides, approximately 10–30 amino acid residues in length, are gen-erated in endosomal vesicles. The endosomal vesicles can then fuse with exocytic vesicles containing class II MHC mol-ecules. Induction of CMI involves sequence of events, which is explained below.
Induction of CMI begins with presentation of foreign antigen by APCs to T lymphocytes. T-cell receptors (TCRs), which are antigen recognition receptors, are present on T lymphocytes, and recognize foreign antigen and a self-MHC molecule on the surface of APCs. Subsequently, the sensitized T lymphocytes undergo blast transformation, clonal proliferation, and dif-ferentiation into memory cells and effector cells, such as Th, Tc, Td, and Ts. Finally, the lymphokines, which are biologically active products responsible for various manifestations of CMI, are released by the activated lymphocytes.
T cells recognize antigens only when presented with MHC mol-ecules. The combination of foreign antigen and class I MHC molecule is recognized by CD81 cells. These CD81 cells after recognition differentiate into Tc and Ts lymphocytes. On the other hand, CD41 cells recognize the combination of antigen and class II MHC antigen, after which they are differentiated into Th and Td cells. The class II MHC molecules are synthe-sized, as for other membrane glycoprotein, in the rough endo-plasmic reticulum and then proceed out through the Golgi apparatus. A third polypeptide, the invariant chain (Ii), protects the binding site of the class II dimer until the lowered pH of the compartment created after fusion with an endosomal vesicle causes a dissociation of the Ii chain. The MHC class II peptide antigen complex is then transported to the cell surface for display and recognition by a TCR of a CD4 T cell.
The lymphocyte recognizes antigen and class I MHC mol-ecule and gets attached to the target cells. Endogenous anti-gens such as cytosolic viral proteins synthesized in an infected cell are processed for presentation by class I MHC molecule. In brief, cytosolic proteins are broken down by a peptidase complex known as the proteasome. The cytosolic peptides gain access to nascent MHC class I molecules in the rough endo-plasmic reticulum via peptide transporter systems (transport-ers associated with antigen processing; TAPs). The TAP genes are also encoded in the MHC.
The binding groove of the class I molecule is more constrained than that of the class II molecule; for that reason, shorter peptides are found in class I than in class II MHC molecules.
This stimulates Tc lymphocytes to release cytokines, resulting in the lysis of the target cells. The T cells then detach from the target cells and attach with other target cells, and the same pro-cess is repeated. Interferon-gamma synthesized and secreted by Tc lymphocytes possibly also contributes for macrophage acti-vation in some way.