Major histocompatibility complex (MHC)

The Major Histocompatibility Complex (MHC) is a set of proteins found on the surface of cells that play a vital role in the immune system, particularly in helping the body recognize foreign molecules. MHC proteins present fragments of antigens to T-cells, which trigger immune responses. Due to its high level of variability, MHC allows the immune system to distinguish between self and non-self molecules, a key feature in defending the body against infections.
Table of Contents
Structure of MHC
MHC molecules are specialized glycoproteins located on cell surfaces, involved in presenting antigenic peptides to T-cells. They are divided into two major classes—Class I and Class II—each having distinct structural characteristics and functions.
MHC Class I

Structure: Major Histocompatibility Complex Class I molecules consist of a large alpha chain (α) and a smaller beta-2 microglobulin (β2m). The alpha chain includes three domains (α1, α2, and α3), with the α1 and α2 domains forming the peptide-binding groove, which holds peptides that are 8-10 amino acids long.
Expression: Major Histocompatibility Complex Class I molecules are present on the surface of nearly all nucleated cells.
Peptide binding: They present peptides generated inside the cell, known as endogenous antigens, to CD8+ cytotoxic T-cells.
Function: The primary role is to identify and signal the presence of infected or abnormal cells, such as those harboring viruses or cancer, prompting CD8+ T-cells to destroy the affected cells.
MHC Class II

Structure: Major Histocompatibility Complex Class II molecules are made up of two chains, alpha (α) and beta (β), each having two domains (α1, α2, β1, β2). The α1 and β1 domains form the peptide-binding groove, which accommodates peptides 13-18 amino acids in length.
Expression: Major Histocompatibility Complex Class II molecules are primarily found on professional antigen-presenting cells (APCs) like dendritic cells, macrophages, and B-cells.
Peptide binding: These molecules present antigens derived from pathogens taken up from outside the cell, called exogenous antigens, to CD4+ helper T-cells.
Function: Major Histocompatibility Complex Class II molecules activate CD4+ T-cells, which in turn help coordinate immune responses, such as aiding B-cells in producing antibodies.
Types of MHC
MHC Class I
Major Histocompatibility Complex Class I molecules are encoded by three primary genes in humans: HLA-A, HLA-B, and HLA-C.
These molecules present peptides from intracellular pathogens, such as viruses, and are crucial in identifying and eliminating infected cells.
MHC Class II
Major Histocompatibility Complex Class II molecules are encoded by genes like HLA-DP, HLA-DQ, and HLA-DR.
They specialize in presenting antigens from pathogens external to the cell, playing a vital role in activating immune responses against bacteria and other extracellular organisms.
MHC Class III
MHC Class III molecules, although less well-known, include components related to the complement system and other immune-related processes but do not play a direct role in antigen presentation.
Functions of MHC
Antigen Presentation
The main function of MHC molecules is to display peptide fragments from antigens to T-cells, initiating immune responses. This is essential for detecting infected cells or those showing signs of disease, like cancerous cells, and eliminating them.
Recognition of Self vs. Non-Self
MHC molecules help the immune system differentiate between the body’s own proteins and foreign ones. When a foreign antigen is presented by MHC molecules, the immune system mounts an attack. When self-antigens are presented, the immune system usually tolerates them, avoiding autoimmune responses.
T-cell Activation
MHC Class I molecules activate CD8+ cytotoxic T-cells, which destroy infected cells. On the other hand, MHC Class II molecules activate CD4+ helper T-cells, which aid in the coordination of immune activities, such as stimulating B-cells to produce antibodies. Both types are essential for the body’s adaptive immune responses.
Role in Transplant Rejection
Variations in MHC molecules between individuals are a key reason for organ transplant rejection. The immune system recognizes the differences in MHC molecules from donor tissue, often leading to a rejection response.
Immune System Diversity
The diversity of MHC genes ensures that different individuals can present a wide range of antigens, making the immune system more adaptable to new infections. This genetic variability is critical for the survival of populations, as it increases the likelihood that some individuals will resist certain pathogens.
Conclusion
In summary, Major histocompatibility complex molecules are crucial components of the immune system, enabling the recognition and response to foreign antigens. By presenting antigens to T-cells, they help activate immune responses, maintain self-tolerance, and contribute to immune diversity. MHC Class I and Class II serve distinct but complementary roles, with Class I presenting internal antigens to cytotoxic T-cells and Class II presenting external antigens to helper T-cells. Understanding the role of MHC is important in immunology, infectious disease, and transplantation science.
Frequently Asked Questions (FAQ)
What is the role of MHC in transparent rejection?
Variations in MHC molecules between individuals are a key reason for organ transplant rejection. The immune system recognizes the differences in MHC molecules from donor tissue, often leading to a rejection response.
Write the main function of MHC ?
The main function of MHC molecules is to display peptide fragments from antigens to T-cells, initiating immune responses. This is essential for detecting infected cells or those showing signs of disease, like cancerous cells, and eliminating them.
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