MHC Molecule and Autoimmunity with Examples and Diagrams

Updated:

MHC molecules, or major histocompatibility complex molecules, are a group of proteins that play a vital role in the immune system. They are found on the surface of most cells in the body and help the immune system to recognize and respond to foreign invaders, such as bacteria, viruses, parasites, and cancer cells.

MHC molecules are encoded by a set of genes called the human leukocyte antigen (HLA) system, which is located on chromosome 6 of the human genome. The HLA system is one of the most diverse and polymorphic gene regions in humans, meaning that there are many different variants or alleles of each gene. This diversity ensures that each individual has a unique set of MHC molecules that can present a wide range of antigens to the immune system.

MHC molecules can be divided into three classes: class I, class II, and class III. Class I and class II molecules are involved in antigen presentation, while class III molecules are involved in other immune functions, such as inflammation and complement activation.

Class I MHC molecules are expressed on almost all nucleated cells in the body and present antigens derived from intracellular sources, such as viral or bacterial proteins. Class I MHC molecules bind to peptides that are generated by the degradation of these proteins in the cytoplasm and transport them to the cell surface. There, they interact with T cells that have a receptor called CD8. CD8+ T cells are also known as cytotoxic T cells or killer T cells because they can destroy infected or abnormal cells by releasing toxic substances.

Class II MHC molecules are expressed mainly on specialized cells called antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells. Class II MHC molecules present antigens derived from extracellular sources, such as bacterial toxins or allergens. Class II MHC molecules bind to peptides that are generated by the degradation of these proteins in specialized compartments called endosomes and lysosomes and transport them to the cell surface. There, they interact with T cells that have a receptor called CD4. CD4+ T cells are also known as helper T cells because they can activate other immune cells by releasing cytokines.

The interaction between MHC molecules and T cell receptors is essential for the activation and differentiation of T cells and the initiation of adaptive immune responses. However, this interaction also has implications for self-tolerance and autoimmunity. Self-tolerance is the ability of the immune system to distinguish between self and non-self antigens and avoid attacking healthy tissues. Autoimmunity is the loss of self-tolerance and the development of immune responses against self-antigens, leading to chronic inflammation and tissue damage.

The development of self-tolerance and autoimmunity is influenced by several factors, including genetic predisposition, environmental triggers, and epigenetic modifications. One of the most important genetic factors is the HLA system itself. Certain HLA alleles or combinations of alleles are associated with an increased or decreased risk of developing various autoimmune disorders, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, celiac disease, and psoriasis. The exact mechanisms by which HLA genes influence autoimmunity are not fully understood but may involve altered antigen presentation, T cell selection, or regulation.

In this article, we will explore the functions of MHC molecules in more detail and discuss how they are involved in autoimmunity with examples and diagrams. We will also review some of the current research and challenges in this field.