Major Histocompatibility Complex (MHC) refers to a group of genetic proteins present on the surface of all nucleated cells and platelets. In humans, these proteins are known as HLA (Human Leukocyte Antigens) because they were first discovered on leukocytes.
The main function of MHC proteins is to help the immune system distinguish self from non-self. They are essential for antigen presentation, immune regulation and tissue transplantation.
Location and Genetic Basis
MHC genes are located on the short arm (p) of chromosome 6. They occupy four major regions or loci:
- HLA-A
- HLA-B
- HLA-C
- HLA-D
MHC genes are highly polymorphic, meaning many variations (alleles) exist in the population. This explains why matching organ donors and recipients is difficult. The letter “w” in some alleles (e.g., Bw15, Cw4, Dw3) represents international workshop terminology.
Classes of MHC Proteins
MHC proteins are divided into three classes based on their structure and function:
1. Class I MHC
- Includes: HLA-A, HLA-B, HLA-C
- Present on: all nucleated cells
- Recognized by: CD8+ cytotoxic T cells
- Function: Present intracellular antigens (e.g., viral peptides)
2. Class II MHC
- Includes: HLA-D region (DR, DQ, DP)
- Present on: antigen-presenting cells (APCs) such as B cells, macrophages and dendritic cells
- Recognized by: CD4+ helper T cells
- Function: Present extracellular antigens after phagocytosis
3. Class III MHC
- Includes certain complement proteins (e.g., C2, C4)
- Not directly involved in antigen presentation
- Still located within the MHC gene complex on chromosome 6
MHC Polymorphism
Because Class I and Class II MHC genes have many alleles, they are extremely diverse. Examples: HLA-A1, HLA-A2, HLA-A3, etc.
This diversity ensures better immune protection at the population level, but it also makes organ transplantation more complicated.
Role of MHC Proteins
1. Antigen Presentation
MHC proteins help macrophages and other APCs present foreign antigens to T cells.
- Class I MHC → presents to CD8+ cytotoxic T cells
- Class II MHC → presents to CD4+ helper T cells
This interaction is essential for initiating both cellular and humoral immune responses.
2. Organ Transplantation
Matching donor and recipient HLA types is critical for successful transplantation. If the recipient’s immune system recognizes donor MHC as foreign, it mounts an immune response leading to rejection.
Both humoral and cell-mediated immunity are involved in graft rejection.
3. Regulation of the Immune System
MHC proteins help coordinate different arms of immunity:
- Class I MHC regulates CD8+ cytotoxic T cell activity, especially in viral infections.
- Class II MHC regulates CD4+ helper T cell functions, influencing antibody production and inflammation.
4. Disease Associations
Several diseases show strong association with specific HLA alleles. These include:
- Inflammatory disorders: Ankylosing spondylitis (HLA-B27)
- Autoimmune diseases: Rheumatoid arthritis, insulin-dependent diabetes mellitus
- Inherited metabolic disorders: Idiopathic haemochromatosis
The exact reason behind these associations is not fully understood but may involve altered immune regulation.
Detailed Notes:
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