Peptide Binding to MHC Molecules

Peptide Binding to MHC Molecules

• Anchor residues play a crucial role in peptide binding to MHC molecules by fitting into specific pockets, allowing the peptide to bind stably.

Class 2 MHC Molecule

• The two residues projected at the top of the peptide bound to class 2 MHC molecule interact with the T-cell receptor.

Peptide Acquistion by MHC Molecules

• MHC molecules acquire their peptide cargo through proteasomal processing and transport of peptides from the cytosol into the endoplasmic reticulum.

Space-Filling Model of Peptide Bound to Class 2 MHC Molecule

• The space-filling model of the peptide bound to class 2 MHC molecule depicts the peptide nestled in the peptide-binding groove, highlighting the close interactions between the peptide and the MHC molecule.

MHC-Restricted T Cells

• MHC-restricted T cells recognize cell-associated antigens and not cell-free antigens because they are activated by peptides presented by MHC molecules on antigen-presenting cells (APCs).

Presentation of Foreign Antigens

• MHC molecules do not constantly present foreign antigens despite the likely greater quantity of self-proteins in an APC because immune tolerance mechanisms, such as thymic selection and peripheral tolerance, prevent immune responses to self-antigens.

Immune Tolerance

• The development of immune responses to self-antigens presented by MHC molecules is prevented by central tolerance mechanisms, such as thymic deletion and negative selection, and peripheral tolerance mechanisms, such as regulatory T cells.

Peptide Binding Specificity

• The unique binding specificity of each T cell to a single peptide is due to the ability of MHC molecules to bind to a specific peptide sequence, allowing each T cell to respond to a unique peptide.

Peptide Presentation by MHC Molecules

• After an MHC molecule has acquired a peptide, it will display the peptide long enough for a T cell to initiate a response because peptide-loaded MHC molecules are stably expressed on the cell surface.

Cell Surface Expression of MHC Molecules

• Only peptide-loaded MHC molecules are stably expressed on the cell surface for recognition by T cells because empty MHC molecules are unstable and rapidly degraded.

Immune Surveillance

• The presentation of peptides from different cellular compartments by MHC molecules facilitates immune surveillance for microbes in different locations.

Importance of Peptide Binding

• It is essential that MHC molecules bind only peptides instead of intact protein antigens because peptides are more susceptible to proteolysis and can be easily transported and processed by the immune system.