Antigen processing
Also known as: antigen processing and presentation
Antigen processing is the pathway by which cells break down proteins into peptide fragments and load them onto MHC molecules for display to T cells. Intracellular antigens are presented on MHC class I to CD8+ T cells, while extracellular antigens are presented on MHC class II to CD4+ T cells.
Antigen processing is how the immune system converts whole proteins into displayable fragments that T cells can recognize. T cells cannot see intact pathogens; they recognize short peptides bound to major histocompatibility complex (MHC) molecules on a cell's surface. Processing describes the degradation of protein antigens and the loading of the resulting peptides onto MHC.
The MHC class I (endogenous) pathway handles proteins made inside the cell, such as viral proteins in an infected cell. Cytosolic proteins are degraded by the proteasome, and the peptides are pumped into the endoplasmic reticulum by the TAP transporter, where they load onto MHC class I. Nearly all nucleated cells express MHC class I, and the peptide-MHC I complex is surveyed by CD8+ cytotoxic T cells, which kill cells displaying foreign peptides.
The MHC class II (exogenous) pathway handles material taken up from outside the cell. Professional antigen-presenting cells — dendritic cells, macrophages, and B cells — endocytose antigens and degrade them in acidified endosomes and lysosomes. MHC class II travels with an invariant chain that blocks its groove until the CLIP fragment is exchanged for antigenic peptide, and the complex is displayed to CD4+ helper T cells. Dendritic cells can also cross-present extracellular antigens on MHC class I, which is essential for activating cytotoxic responses against viruses and tumors.
The USMLE Step 1 exam tests antigen processing in its immunology section, expecting candidates to match each pathway to its compartment, machinery (proteasome and TAP versus endosomes and invariant chain), MHC class, and responding T-cell type.
Key takeaways
- Antigen processing degrades proteins into peptides and loads them onto MHC molecules for T-cell recognition.
- The endogenous pathway uses the proteasome and TAP to load cytosolic peptides onto MHC class I for CD8+ T cells.
- The exogenous pathway degrades endocytosed antigens and loads them onto MHC class II for CD4+ T cells.
- MHC class I appears on nearly all nucleated cells; MHC class II is restricted to professional antigen-presenting cells.
- USMLE Step 1 tests the compartments, transporters, and T-cell pairings of both pathways.