Unit 3: Antigen Recognition and Processing

Table of Contents

T-cells cannot recognize "free" or "naked" antigens. They can only recognize antigens that have been broken down (processed) and "presented" on the surface of another cell by a special molecule called MHC.

1. MHC Molecules (Class I and Class II)

MHC (Major Histocompatibility Complex) molecules are a set of proteins on the cell surface that display antigens. In humans, they are also called HLA (Human Leukocyte Antigens).

Comparison of MHC-I and MHC-II

Feature MHC Class I MHC Class II
Found on: All nucleated cells (i.e., every cell in your body except red blood cells). Only on "Professional" Antigen-Presenting Cells (APCs) (e.g., Dendritic cells, Macrophages, B-cells).
Presents antigen to: CD8+ T-cells (Cytotoxic T-lymphocytes, or CTLs). CD4+ T-cells (Helper T-lymphocytes, or TH).
Source of antigen: Endogenous (internal) antigens (e.g., viral proteins, proteins from a tumor). Exogenous (external) antigens (e.g., bacteria that have been "eaten" by the cell).
Analogy: A "health status" report. Shows what's being made *inside* the cell. A "scout's report." Shows what has been found *outside* the cell.
Exam Tip: Use the "Rule of 8" to remember the T-cell interaction:

2. Antigen Processing and Presentation

Antigen processing is the process of breaking down a pathogen (or its proteins) into small peptides. Antigen presentation is the process of binding these peptides to MHC molecules and displaying them on the cell surface for T-cells to "see."

There are two distinct pathways, depending on where the antigen comes from.

3. The Endogenous (Cytosolic) Pathway - MHC Class I

This pathway is used by *any* cell to report an *internal* infection (like a virus).

  1. Production: A virus infects a cell and forces it to make viral proteins in the cytosol.
  2. Processing: Some of these proteins are tagged for destruction and fed into the proteasome (a "protein shredder"), which chops them into small peptides.
  3. Transport: The peptides are transported from the cytosol into the endoplasmic reticulum (ER).
  4. Loading: Inside the ER, the peptides are loaded onto newly made MHC Class I molecules.
  5. Presentation: The peptide-MHC-I complex is transported to the cell surface and displayed.
  6. Recognition: A CD8+ Cytotoxic T-cell recognizes this complex as "foreign" (e.g., "viral"), becomes activated, and kills the infected cell.

Summary: Internal antigen → Proteasome → ER → MHC-I → Presented to CD8+ T-cell → Cell is killed.

4. The Exogenous (Endocytic) Pathway - MHC Class II

This pathway is used only by *professional APCs* (like macrophages) to report an *external* invader.

  1. Engulfment: An APC "eats" an external pathogen (like a bacterium) via phagocytosis. The pathogen is now inside a vesicle called a phagosome.
  2. Processing: The phagosome fuses with a lysosome. The enzymes inside chop the pathogen into small peptides.
  3. Loading: Meanwhile, MHC Class II molecules are made in the ER and sent to a separate vesicle. This vesicle fuses with the peptide-filled phagolysosome. The peptides are loaded onto the MHC-II molecules.
  4. Presentation: The peptide-MHC-II complex is transported to the cell surface and displayed.
  5. Recognition: A CD4+ Helper T-cell recognizes this complex as "foreign." It becomes activated and begins to "help" the immune response by releasing cytokines (to activate B-cells and macrophages).

Summary: External antigen → Phagosome/Lysosome → MHC-II → Presented to CD4+ T-cell → Immune response is activated.