MHC II

Major Histocompatibility Complex Class II (MHC II)

The Major Histocompatibility Complex Class II (MHC 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 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: the α1 and α2 domains for the alpha chain, and the β1 and β2 domains for the beta chain. The peptide-binding groove, which accommodates peptides of 10-30 amino acids in length, is formed by the α1 and β1 domains.

Function

The primary function of MHC II molecules is to present exogenous antigens to CD4+ T cells. This 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 peptide fragments within endosomal/lysosomal compartments. 3. Peptide Loading: MHC II molecules are synthesized in the endoplasmic reticulum and transported to the endosomal compartments, where they bind to the processed peptides. 4. Antigen Presentation: The peptide-MHC II complexes are transported to the cell surface, where they can be recognized by CD4+ T cells.

Role in Immune Response

MHC II molecules are essential for the activation of CD4+ T helper cells, which in turn help activate B cells to produce antibodies and cytotoxic T cells to kill infected cells. This interaction is critical for the coordination and regulation of the adaptive immune response.

Genetic Organization

The genes encoding MHC II molecules are located on chromosome 6 in humans, within the human leukocyte antigen (HLA) complex. The main MHC II genes include HLA-DP, HLA-DQ, and HLA-DR, each of which has multiple alleles contributing to the diversity of the immune response.

Clinical Significance

MHC II molecules are involved in various immune-related diseases and conditions, including:

- Autoimmune Diseases: Aberrant expression or function of MHC II molecules can lead to autoimmune diseases such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. - Transplantation: MHC II compatibility is crucial for organ transplantation, as mismatches can lead to graft rejection. - Infectious Diseases: The ability of MHC II molecules to present antigens from pathogens is vital for the immune system to recognize and respond to infections.

Also see

- Major Histocompatibility Complex - Antigen-Presenting Cell - CD4+ T Cell - Adaptive Immune System - Human Leukocyte Antigen