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The Major Histocompatibility-I System: the Activation of Naïve CD8 (T8) Lymphocytes by Dendritic Cells
Resource Type: Visual: Animation
Publication Date: 8/25/2009
Animation 1

Animation 1
Animation 2

Animation 2
Authors
Gary Kaiser
Biology Department
The Community College of Baltimore County, Catonsville Campus
Baltimore, MD 21228
USA
Email: gkaiser@ccbcmd.edu
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-I molecules are designed to enable the body to recognize infected cells and tumor cells and destroy them with cytotoxic T lymphocytes (CTLs). CTLs are effector defense cells derived from naïve CD8 (T8) lymphocytes, but first these naïve CD8 (T8) lymphocytes must be activated by antigen-presenting cells called dendritic cells.

MHC-I molecules are:
  • made by all nucleated cells in the body;
  • possess a deep groove that can bind peptide epitopes, typically 8 to 11 amino acids long, from endogenous antigens; and
  • present MHC-I–peptide complexes to CD8 (T8) lymphocytes that have a complementary-shaped T-cell receptor (TCR).
Endogenous antigens are proteins found within the cytosol of human cells. Examples of endogenous antigens include:
  • viral proteins produced during viral replication,
  • proteins produced by intracellular bacteria such as Rickettsias and Chlamydias during their replication,
  • proteins that have escaped into the cytosol from the phagosome of phagocytes such as antigen-presenting cells,
  • tumor antigens produced by cancer cells, and
  • self-peptides from host cellular proteins.

Dendritic cells are antigen-presenting cells (APCs) that are able to activate naïve CD8 (T8) lymphocytes and naïve CD4 (T4) lymphocytes. Dendritic cells produce both MHC-I molecules (to present endogenous antigens to naïve CD8 (T8) lymphocytes) and MHC-II molecules (to present exogenous antigens to naïve CD4 (T4) lymphocytes.) 

The first of the two animations illustrates an antigen-presenting dendritic cell processing a virus for presentation of viral epitopes to naïve CD8 (T8) 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, some of the viral proteins escape from the phagolysosome into the cytosol to become endogenous antigens.  

Slide 4 shows one of these endogenous antigens passing through a proteasome where it is degraded into a series of peptides.

In slide 5, the peptides are transported into the rough endoplasmic reticulum by a transporter protein called TAP (transporter associated with antigen processing). The peptides then bind to the grooves of newly synthesized MHC-I molecules.

Slide 6 shows the endoplasmic reticulum transporting the MHC-I molecules with bound peptides to the Golgi complex and the Golgi complex, in turn, transporting the MHC-I–peptide complexes by way of an exocytic vesicle to the cytoplasmic membrane where they become anchored. Here, the peptide and MHC-I–peptide complexes can be recognized by naïve CD8 (T8) lymphocytes with T-cell receptors and CD8 molecules having a complementary shape. 

The second animation illustrates a naïve CD8 (T8) lymphocyte recognizing epitope–MHC-I on an antigen-presenting dendritic cell by way of its TCR and CD8 molecules.

Slides 1 and 2 show a naïve CD8 (T8) lymphocyte using its TCR and CD8 to recognize an MHC-I molecule with attached peptide being presented by an antigen-presenting dendritic cell.

Slides 3 and 4 show the binding of costimulatory molecules, such as B7, CD40, LFA-3, and ICAM-1, on the dendritic cell binding to corresponding ligand molecules (CD28, CD40L, CD2, and LFA-1) on the naïve CD8 (T8) 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 CD8 (T8) lymphocyte cell enabling its eventual differentiation into effector CD8 (T8) lymphocytes such as cytotoxic T lymphocytes (CTLs).

Macromedia Flash Professional 8 was used in constructing this animation. Illustrations were drawn using Adobe Illustrator 10.0.3 and imported into Flash 8.

References. 

1.  Abbas, A. K., A. H. Lichtman, and S. Pillai. 2007. Cellular and molecular immunology, 6th ed. Saunders/Elsevier Publishing, Philadelphia, PA.

2.  Delves, P. J., S. J. Martin, D. R. Burton, and I. M. Roitt. 2006. Roitt’s essential immunology, 11th ed. Blackwell Publishing, Malden, MA.