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.

Learn about how peptides bind to major histocompatibility complex (MHC) molecules and the recognition by T cells. Explore the crystal structures of MHC molecules and the arrangement of peptides in the peptide-binding clefts.