HLA-A

1. 본문

HLA-A (Human Leukocyte Antigen A) is a gene that plays a crucial role in the human immune system. It belongs to the Major Histocompatibility Complex (MHC) class I family, which is a group of genes that encode cell surface proteins responsible for regulating the immune system. Here's a breakdown of HLA-A:
Function:

• Antigen Presentation: HLA-A's primary function is to present peptide fragments (short pieces of proteins) to the immune system, specifically to cytotoxic T cells (CD8+ T cells). These peptides can be derived from:
• Self-proteins: Normal proteins produced by the cell.
• Non-self proteins: Foreign peptides from viruses, bacteria, or other intracellular pathogens, or abnormal proteins produced by cancerous cells.
• Immune Response Activation/Regulation: By presenting these peptides, HLA-A helps cytotoxic T cells distinguish between healthy cells and infected or cancerous cells. When a T cell recognizes a non-self peptide presented by HLA-A, it triggers an immune response to eliminate the affected cell.
• Immune System Differentiation: The immune system utilizes HLAs to distinguish between the body's own cells ("self") and foreign invaders ("non-self").

• Heterodimer: HLA-A is a heterodimeric molecule, meaning it consists of two different protein chains:
• Heavy Chain (α chain): Encoded by the HLA-A gene located on chromosome 6. This chain is anchored in the cell membrane.
• Light Chain (β2-microglobulin): Encoded by the B2M gene on chromosome 15.
• Peptide-Binding Groove: The α chain has three domains. The α1 and α2 domains form a groove where the peptide fragments bind. The α3 domain is important for interaction with CD8+ T cells.
• Exons: The HLA-A gene contains 8 exons. Exons 2 and 3 are particularly important as polymorphisms (variations) in these regions determine the peptide-binding specificity.

• High Polymorphism: HLA-A is one of the most polymorphic genes in the human genome, meaning there are many different versions (alleles) of this gene within the population. As of March 2022, there are over 7,452 known HLA-A alleles, that encode for over 4,305 active proteins.
• Population Diversity: This extensive variation contributes to the diversity of the immune system across individuals, enhancing the ability to respond to a wide range of pathogens.
• Transplant Rejection: The high variability of HLA-A is a major factor in transplant rejection. Matching HLA-A alleles between donor and recipient is critical for successful transplantation to minimize the risk of the recipient's immune system attacking the transplanted tissue.

• Because each HLA-A gene binds to different peptides, certain HLA-A alleles are associated with increased risk or severity of certain diseases.
• Infectious Diseases: Variations in the HLA-A gene can influence the immune response to infections, including malaria, HIV, and SARS-CoV-2 (COVID-19).
• Autoimmune Diseases: Certain HLA-A alleles are associated with an increased risk of developing autoimmune diseases.
• Cancer: HLA-A can present tumor-derived peptides, allowing the immune system to recognize and potentially eliminate cancer cells. Some cancer cells may have altered HLA-A expression, which can affect the immune response.

• The HLA-A gene is located on the short arm of chromosome 6 (6p21.3).
• The protein encoded by the HLA-A gene is approximately 365 amino acids long.