MHC and Antigen Presentation: Videos & Practice Problems

MHC Class I and MHC Class II molecules differ in several key aspects. MHC Class I molecules consist of a single polypeptide chain associated with β2-microglobulin and present intracellular antigens, typically from viruses, to cytotoxic T cells (Tc cells). These antigens are processed in the proteasome and transported to the endoplasmic reticulum (ER) via the TAP complex. In contrast, MHC Class II molecules are heterodimers composed of two polypeptide chains and present extracellular antigens to T helper cells (Th cells). These antigens are taken up by the cell, degraded in lysosomes, and then loaded onto MHC Class II molecules. The structural differences include Class I's single chain and Class II's heterodimer, with Class II binding longer peptide sequences (12-20 amino acids).

MHC Class I molecules present antigens to cytotoxic T cells (Tc cells) through a multi-step process. First, intracellular pathogens, such as viruses, are degraded into small peptide fragments by the proteasome. These fragments are then transported into the endoplasmic reticulum (ER) by the TAP complex. In the ER, the peptides bind to MHC Class I molecules, which consist of a single polypeptide chain and β2-microglobulin. The MHC Class I-peptide complex is then transported to the cell surface, where it can be recognized by Tc cells. This recognition activates the Tc cells to destroy the infected cell, thereby eliminating the intracellular pathogen.

MHC Class II molecules play a crucial role in the immune response by presenting extracellular antigens to T helper cells (Th cells). These antigens are typically derived from pathogens that have been phagocytosed by antigen-presenting cells (APCs). Once inside the cell, the pathogen is degraded in lysosomes into peptide fragments. Simultaneously, MHC Class II molecules are synthesized in the endoplasmic reticulum (ER) and complexed with the invariant chain (Ii). This complex is transported to the lysosome, where the invariant chain is cleaved to form CLIP, which is then replaced by the antigenic peptide. The MHC Class II-peptide complex is then transported to the cell surface, where it can be recognized by Th cells, leading to their activation and subsequent immune response coordination.

The TAP (Transporter Associated with Antigen Processing) complex is a crucial component in the antigen presentation pathway of MHC Class I molecules. It is located in the membrane of the endoplasmic reticulum (ER) and is responsible for transporting peptide fragments generated by the proteasome from the cytosol into the ER. These peptides are typically 8-10 amino acids long and are derived from intracellular pathogens. Once inside the ER, these peptides bind to MHC Class I molecules, which are then transported to the cell surface to present the antigen to cytotoxic T cells (Tc cells). This process is essential for the immune system to recognize and eliminate infected cells.

MHC molecules are essential for adaptive immunity as they present antigens to T cells, enabling the immune system to recognize and respond to pathogens. MHC Class I molecules present intracellular antigens to cytotoxic T cells (Tc cells), leading to the destruction of infected cells. MHC Class II molecules present extracellular antigens to T helper cells (Th cells), which then activate other immune cells, such as B cells and macrophages, to mount a coordinated immune response. This antigen presentation is crucial for the specificity and memory of the adaptive immune system, allowing it to effectively target and remember specific pathogens for faster responses upon re-exposure.