MHC Class II

Major Histocompatibility Complex Class II

The Major Histocompatibility Complex Class II (MHC Class II) molecules are a class of major histocompatibility complex proteins that are primarily expressed on the surface of antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells. These molecules play a crucial role in the immune system by presenting processed antigens to CD4+ T helper cells, thereby initiating an adaptive immune response.

Structure

MHC Class II molecules are heterodimeric proteins composed of two non-covalently associated polypeptide chains: the alpha (α) chain and the beta (β) chain. Each chain consists of two domains:

• α1 and α2 domains: These domains form the peptide-binding groove, which accommodates peptides of 10-30 amino acids in length.
• β1 and β2 domains: The β1 domain contributes to the peptide-binding groove, while the β2 domain interacts with the CD4 co-receptor on T helper cells.

The peptide-binding groove of MHC Class II molecules is open at both ends, allowing longer peptides to bind compared to MHC Class I molecules.

Function

MHC Class II molecules are essential for the presentation of extracellular antigens. The process involves several steps:

1. Antigen Uptake: Antigen-presenting cells internalize extracellular proteins through endocytosis or phagocytosis. 2. Antigen Processing: The internalized proteins are degraded into peptides within endosomal/lysosomal compartments. 3. Peptide Loading: MHC Class II molecules are synthesized in the endoplasmic reticulum and transported to the endosomal compartments, where they bind to the processed peptides. 4. Surface Expression: The peptide-MHC Class II complexes are transported to the cell surface, where they can be recognized by CD4+ T helper cells.

Role in Immune Response

MHC Class II molecules are pivotal in the activation of CD4+ T helper cells, which are essential for orchestrating the adaptive immune response. Upon recognition of the peptide-MHC Class II complex, CD4+ T cells become activated and proliferate, leading to the secretion of cytokines that help activate B cells, cytotoxic T cells, and other immune cells.

Genetic Diversity

The genes encoding MHC Class II molecules are highly polymorphic, which contributes to the diversity of the immune response. The primary genes include HLA-DP, HLA-DQ, and HLA-DR in humans. This genetic variability allows for a wide range of peptides to be presented, enhancing the ability of the immune system to recognize diverse pathogens.

Clinical Significance

MHC Class II molecules are involved in several clinical conditions:

• Autoimmune Diseases: Aberrant expression or presentation of self-antigens by MHC Class II molecules can lead to autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.
• Transplantation: MHC Class II compatibility is crucial in organ transplantation, as mismatches can lead to graft rejection.
• Infectious Diseases: The ability of MHC Class II molecules to present pathogen-derived peptides is critical for the immune response to infections.

Also see

• Major Histocompatibility Complex
• Antigen-Presenting Cell
• CD4+ T Helper Cell
• Autoimmune Disease
• HLA Typing