Antigen Processing and Presentation: Study Notes for Microbiology

Antigen Processing and Presentation

Major Histocompatibility Complex (MHC)

The Major Histocompatibility Complex (MHC) is a set of genes encoding cell surface proteins essential for the acquired immune system to recognize foreign molecules. These molecules are critical for antigen presentation to T cells.

• MHC genetic locus: Refers to the specific location of MHC genes on a chromosome, typically found on chromosome 6 in humans.

• MHC allele: A variant form of an MHC gene, contributing to the diversity of immune responses.

• MHC haplotype: The combination of MHC alleles inherited together from a single parent.

MHC Classes and Their Functions

MHC molecules are classified into two main types, each with distinct roles in antigen presentation:

• MHC Class I: Presents endogenous antigens (from within the cell) to CD8+ cytotoxic T cells.

• MHC Class II: Presents exogenous antigens (from outside the cell) to CD4+ helper T cells.

Key differences between MHC Class I and II:

• MHC Class I is expressed on all nucleated cells; MHC Class II is mainly on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells.

• Peptide binding grooves differ in structure and length.

• Antigen source: Class I presents intracellular antigens; Class II presents extracellular antigens.

Antigen Recognition by T Cells

T cells recognize antigens only when presented by MHC molecules:

• CD8+ T cells: Recognize antigens presented by MHC Class I.

• CD4+ T cells: Recognize antigens presented by MHC Class II.

MHC Polymorphism

MHC polymorphism refers to the high variability in MHC genes among individuals, which enhances the ability of populations to respond to diverse pathogens.

• Polymorphism is concentrated in the peptide-binding regions.

• Ensures a wide range of antigen presentation capabilities.

Peptide Binding and Structural Differences

The structure of MHC molecules determines the type and length of peptides they bind:

• MHC Class I binds shorter peptides (8-10 amino acids).

• MHC Class II binds longer peptides (13-18 amino acids).

• Structural differences in the peptide-binding groove reflect these binding preferences.

Antigen Processing Pathways

Antigen processing involves the generation of peptide fragments for presentation by MHC molecules:

• Endogenous pathway (MHC Class I): Cytosolic proteins are degraded by the proteasome, transported into the ER by TAP, and loaded onto MHC Class I.

• Exogenous pathway (MHC Class II): Extracellular proteins are endocytosed, degraded in endosomes, and loaded onto MHC Class II.

Invariant Chain and Peptide Loading

The invariant chain blocks the peptide-binding groove of MHC Class II in the ER, preventing premature peptide binding. It is degraded in endosomes, allowing antigenic peptides to bind.

Cross Presentation

Cross presentation is the process by which certain APCs present extracellular antigens via MHC Class I, enabling activation of CD8+ T cells against pathogens not directly infecting APCs.

Tapasin and HLA-DM

Both tapasin and HLA-DM facilitate optimal peptide loading onto MHC molecules:

• Tapasin assists in loading high-affinity peptides onto MHC Class I.

• HLA-DM catalyzes peptide exchange on MHC Class II, ensuring stable peptide-MHC complexes.

Disruption of Antigen Processing by Viruses

Certain viruses, such as Human Cytomegalovirus, can interfere with MHC Class I antigen processing to evade immune detection:

• Inhibition of peptide transport into the ER.

• Degradation of MHC Class I molecules.

• Blocking MHC Class I trafficking to the cell surface.

Summary Table: MHC Class I vs. Class II

Feature	MHC Class I	MHC Class II
Expressed on	All nucleated cells	APCs (dendritic cells, macrophages, B cells)
Antigen source	Endogenous (cytosolic)	Exogenous (extracellular)
Recognized by	CD8+ T cells	CD4+ T cells
Peptide length	8-10 amino acids	13-18 amino acids

Key Equations

• Peptide-MHC binding affinity: $K_d = \frac{[MHC][Peptide]}{[MHC:Peptide]}$

Additional info:

• Antigen processing and presentation are central to both innate and adaptive immunity, influencing vaccine design and immunotherapy.