MHC I vs. MHC II

Attribute	MHC I	MHC II
Location	Present on all nucleated cells	Present on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells
Peptide binding	Binds to peptides derived from cytosolic proteins	Binds to peptides derived from extracellular proteins
Antigen presentation	Presents antigens to CD8+ T cells	Presents antigens to CD4+ T cells
Role in immune response	Involved in cytotoxic immune response	Involved in activation of helper T cells

Structure

MHC I and MHC II molecules are both glycoproteins that play a crucial role in the immune system by presenting antigens to T cells. However, they differ in their structure. MHC I molecules are composed of a single polypeptide chain that consists of three domains: α1, α2, and α3. These domains form a peptide-binding groove where antigens are presented. In contrast, MHC II molecules are composed of two polypeptide chains, α and β, each with two domains: α1, α2, β1, and β2. The peptide-binding groove of MHC II molecules is open at both ends, allowing for the presentation of longer peptides compared to MHC I.

Cellular Location

Another key difference between MHC I and MHC II molecules is their cellular location. MHC I molecules are found on the surface of all nucleated cells, including somatic cells and tumor cells. They present endogenous antigens, such as viral or tumor-derived peptides, to CD8+ cytotoxic T cells. In contrast, MHC II molecules are primarily expressed on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. They present exogenous antigens, such as those derived from pathogens, to CD4+ helper T cells.

Antigen Presentation

When it comes to antigen presentation, MHC I and MHC II molecules have distinct roles. MHC I molecules present antigens derived from intracellular pathogens, such as viruses and intracellular bacteria. These antigens are processed in the cytosol and presented on the cell surface to activate CD8+ cytotoxic T cells, which then target and kill infected cells. On the other hand, MHC II molecules present antigens derived from extracellular pathogens that have been engulfed and processed in endosomes or lysosomes. These antigens are presented to CD4+ helper T cells, which help coordinate the immune response.

Peptide Binding Specificity

Both MHC I and MHC II molecules exhibit peptide binding specificity, but they differ in the types of peptides they can bind. MHC I molecules have a preference for short peptides, typically 8-10 amino acids in length, that are derived from cytosolic proteins. These peptides are loaded onto MHC I molecules in the endoplasmic reticulum with the help of the transporter associated with antigen processing (TAP). In contrast, MHC II molecules can bind longer peptides, usually 13-25 amino acids in length, that are derived from extracellular proteins taken up by endocytosis. These peptides are loaded onto MHC II molecules in endosomes or lysosomes.

Regulation of Expression

The expression of MHC I and MHC II molecules is tightly regulated to ensure proper immune responses. MHC I expression is constitutive on most nucleated cells, but it can be upregulated in response to interferons produced during viral infections. This upregulation enhances the presentation of viral antigens to cytotoxic T cells. In contrast, MHC II expression is inducible and is upregulated by cytokines like interferon-gamma and interleukin-4. This allows APCs to efficiently present antigens to helper T cells during an immune response.

Role in Immune Response

Both MHC I and MHC II molecules play critical roles in the immune response, but they do so in different ways. MHC I molecules are essential for the recognition and elimination of infected or abnormal cells by cytotoxic T cells. This process helps prevent the spread of intracellular pathogens and eliminates cancerous cells. On the other hand, MHC II molecules are crucial for activating helper T cells, which coordinate the immune response by providing signals to other immune cells like B cells and cytotoxic T cells. This coordination is essential for mounting an effective immune response against extracellular pathogens.

Conclusion

In conclusion, MHC I and MHC II molecules have distinct attributes that allow them to play complementary roles in the immune system. While MHC I molecules present endogenous antigens to cytotoxic T cells on all nucleated cells, MHC II molecules present exogenous antigens to helper T cells on antigen-presenting cells. Their differences in structure, cellular location, antigen presentation, peptide binding specificity, regulation of expression, and role in the immune response highlight the complexity and sophistication of the immune system's ability to recognize and respond to a wide range of pathogens.