Antigen processing and presentation by MHC-I and MHC-II molecules are critical for T cell recognition of pathogens and self-antigens. MHC-I and MHC-II molecules bind peptides generated by proteolysis, which occurs through different pathways. In the cytosol, the proteasome mediates proteolysis, with the 20S core and 19S regulatory complex facilitating the degradation of ubiquitin-conjugated proteins. The proteasome generates peptides that are translocated into the ER by TAP, where they bind to MHC-I molecules. In endocytic pathways, lysosomal proteolysis generates peptides that are processed and presented by MHC-II molecules. Cross-presentation, where exogenous antigens are processed by MHC-I, is important for CD8⁺ T cell activation. MHC-I and MHC-II molecules have distinct structures that allow them to bind peptides with high affinity. MHC-I molecules have a groove that confines peptides at both ends, while MHC-II molecules allow peptides to overhang. The binding of peptides to MHC-I and MHC-II is facilitated by accessory proteins such as tapasin and calreticulin, which assist in peptide loading and editing. Tapasin interacts with MHC-I and calreticulin to facilitate high-affinity peptide binding, while ERp57 assists in the folding of glycoproteins in the ER. The processing of antigens involves multiple steps, including endocytosis, phagocytosis, and autophagy, which deliver antigens to endosomal compartments where proteolysis occurs. These compartments contain proteases that cleave antigens into peptides that are then presented by MHC molecules. The MHC-II pathway involves the invariant chain (I chain), which directs MHC-II to endosomes and facilitates peptide binding. The I chain is cleaved by proteases in endosomes, releasing CLIP, which is then removed by DM to allow antigenic peptides to bind to MHC-II. The presentation of antigens by MHC-I and MHC-II is influenced by various factors, including the affinity of the peptide for the MHC molecule, the presence of accessory proteins, and the microenvironment of the endosomal compartments. The selection of epitopes for presentation is influenced by the diversity of the T cell repertoire and the processing efficiency of the antigen. The hierarchy of epitopes recognized by the immune system includes immunodominant, subdominant, and cryptic epitopes, with immunodominant epitopes being the most strongly recognized. The processing and presentation of antigens by MHC-I and MHC-II are essential for immune responses, including the recognition of pathogens and the development of tolerance to self-antigens. The mechanisms involved in antigen processing and presentation are complex and involve multiple pathways, including proteolysis, endocytosis, and autophagy. Understanding these pathways isAntigen processing and presentation by MHC-I and MHC-II molecules are critical for T cell recognition of pathogens and self-antigens. MHC-I and MHC-II molecules bind peptides generated by proteolysis, which occurs through different pathways. In the cytosol, the proteasome mediates proteolysis, with the 20S core and 19S regulatory complex facilitating the degradation of ubiquitin-conjugated proteins. The proteasome generates peptides that are translocated into the ER by TAP, where they bind to MHC-I molecules. In endocytic pathways, lysosomal proteolysis generates peptides that are processed and presented by MHC-II molecules. Cross-presentation, where exogenous antigens are processed by MHC-I, is important for CD8⁺ T cell activation. MHC-I and MHC-II molecules have distinct structures that allow them to bind peptides with high affinity. MHC-I molecules have a groove that confines peptides at both ends, while MHC-II molecules allow peptides to overhang. The binding of peptides to MHC-I and MHC-II is facilitated by accessory proteins such as tapasin and calreticulin, which assist in peptide loading and editing. Tapasin interacts with MHC-I and calreticulin to facilitate high-affinity peptide binding, while ERp57 assists in the folding of glycoproteins in the ER. The processing of antigens involves multiple steps, including endocytosis, phagocytosis, and autophagy, which deliver antigens to endosomal compartments where proteolysis occurs. These compartments contain proteases that cleave antigens into peptides that are then presented by MHC molecules. The MHC-II pathway involves the invariant chain (I chain), which directs MHC-II to endosomes and facilitates peptide binding. The I chain is cleaved by proteases in endosomes, releasing CLIP, which is then removed by DM to allow antigenic peptides to bind to MHC-II. The presentation of antigens by MHC-I and MHC-II is influenced by various factors, including the affinity of the peptide for the MHC molecule, the presence of accessory proteins, and the microenvironment of the endosomal compartments. The selection of epitopes for presentation is influenced by the diversity of the T cell repertoire and the processing efficiency of the antigen. The hierarchy of epitopes recognized by the immune system includes immunodominant, subdominant, and cryptic epitopes, with immunodominant epitopes being the most strongly recognized. The processing and presentation of antigens by MHC-I and MHC-II are essential for immune responses, including the recognition of pathogens and the development of tolerance to self-antigens. The mechanisms involved in antigen processing and presentation are complex and involve multiple pathways, including proteolysis, endocytosis, and autophagy. Understanding these pathways is