Major histocompatibility (MHC) molecules enable T lymphocytes to recognize epitopes of antigens and discriminate self from nonself. Unlike B-cell receptors on B lymphocytes that are able to directly bind epitopes on antigens, the T-cell receptors (TCRs) of T lymphocytes can only recognize epitopes, typically short chains of amino acids called peptides, after they are bound to MHC molecules. There are two classes of MHC molecules: MHC-I and MHC-II. MHC-I presents epitopes to CD8 (T8) lymphocytes while MHC-II presents epitopes to CD4 (T4) lymphocytes. MHC-I is composed of an alpha chain and beta 2 microglobulin, and MHC-II is composed of an alpha and beta heterodimer. CD stands for cluster of differentiation, a protocol used for the identification of cell surface molecules present on leukocytes.
MHC-II molecules are designed to enable CD4 (T4) lymphocytes to recognize epitopes of exogenous antigens and discriminate self from nonself.
MHC-II molecules are made by antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B lymphocytes; possess a deep groove that can bind peptide epitopes, typically 10 to 30 amino acids long but with an optimum length of 12 to 16 amino acids, from exogenous antigens; and present MHC-II–peptide complexes to CD4 (T4) lymphocytes that have a complementary-shaped TCR.
Exogenous antigens are antigens that enter from outside the body such as bacteria, fungi, protozoa, and free viruses.
Dendritic cells are APCs that are able to activate naïve CD4 (T4) lymphocytes and naïve CD8 (T8) lymphocytes. Dendritic cells produce both MHC-II molecules (to present exogenous antigens to naïve CD4 (T4) lymphocytes) and MHC-I molecules (to present endogenous antigens to naïve CD8 (T8) lymphocytes.) In this series, the dendritic cell will present antigens to naïve CD4 (T4) lymphocytes for activation of these cells.
The first of the two animations illustrates an antigen-presenting dendritic cell processing a virus for presentation of viral epitopes to naïve CD4 (T4) lymphocytes.
Slide 1 shows a dendritic cell engulfing a virus and placing it in a phagosome.
Slide 2 shows a lysosome fusing with the phagosome and the degradation of the virus.
In slide 3, viral proteins are degraded by cellular proteases into a series of peptides within the phagolysosome.
Slide 4 shows MHC-II molecules being synthesized in the endoplasmic reticulum and transported to the Golgi complex. Once assembled, within the endoplasmic reticulum, a protein called the invariant chain (Ii) attaches to the peptide-binding groove of the MHC-II molecules and in this way prevents peptides designated for binding to MHC-I molecules within the endoplasmic reticulum from attaching to the MHC-II.
In slide 5, the MHC-II molecules with bound Ii chain are transported to the Golgi complex and placed in vesicles.
Slide 6 shows the vesicles containing the MHC-II molecules fusing with the peptide-containing phagolysosome. As the Ii chain is removed, the peptides are now free to bind to the grooves of the MHC-II molecules.
In the final slide, MHC-II molecules with bound peptides are transported to the cytoplasmic membrane where they become anchored. Here, the peptide and MHC-II complexes can be recognized by naïve T4 lymphocytes with TCRs and CD4 molecules having a complementary shape.
The second of the two animations illustrates a naïve CD4 (T4) lymphocyte recognizing epitope–MHC-II on an antigen-presenting dendritic cell.
Slides 1 and 2 show a naïve T4 lymphocyte using its TCR and CD4 to recognize an MHC-II molecule with attached peptide being presented by an antigen-presenting dendritic cell.
Slides 3 and 4 show the binding of adhesion and costimulatory molecules on the dendritic cell binding to corresponding ligand molecules on the naïve CD4 (T4) lymphocyte in order to stabilize the cell-to-cell interaction and activate the naïve cell.
Costimulatory pairs include the interaction between B7 and CD40 molecules on the dendritic cell with, respectively, CD28 and CD154 molecules on CD4 (T4) lymphocytes. These costimulatory interactions serve as second signals needed for the full activation of naïve CD4 (T4) lymphocytes. Other adhesive interactions include the binding of leukocyte function-associated antigen-3 (LFA-3; also known as CD58) and intercellular adhesion molecule-1 (ICAM-1; also known as CD54) molecules on the dendritic cell with CD2 and LFA-1, respectively, on the naïve CD4 (T4) lymphocyte. The longer the dendritic cell and naïve CD4 (T4) lymphocyte remain attached, the greater the likelihood that naïve CD4 (T4) lymphocyte will become fully activated.
Slides 5 and 6 show the dendritic cell-induced activation of the naïve CD4 (T4) lymphocyte cell enabling its eventual differentiation into effector CD4 (T4) lymphocytes such as Th1, Th2, and Th17 cells.
Macromedia Flash Professional 8 was used in constructing this animation. Illustrations were drawn using Adobe Illustrator 10.0.3 and imported into Flash 8.
