MHC/HLA: GENETICS OF IMMUNE RECOGNITION
"๐๐๐ ๐โโ ๐ค๐ช๐ค๐ฅ๐๐ ๐ฃ๐๐ก๐ฃ๐๐ค๐๐๐ฅ๐ค ๐ ๐๐ ๐ ๐ ๐ฅ๐๐ ๐๐ ๐ค๐ฅ ๐ก๐ ๐๐ช๐๐ ๐ฃ๐ก๐๐๐ ๐๐๐๐ ๐๐๐๐๐๐๐๐ค, ๐๐ค๐ค๐๐๐ฅ๐๐๐ ๐๐ ๐๐๐๐ฆ๐๐๐ฅ๐ช ๐๐๐ ๐ฅ๐ฃ๐๐๐ค๐ก๐๐๐๐ฅ๐๐ฅ๐๐ ๐." Dr. Anthony Fauci
๐งฌ The Major Histocompatibility Complex (MHC), called the Human Leukocyte Antigen (HLA) system in humans, is a highly diverse & vital genomic region located on chromosome 6. It encodes molecules essential for adaptive immunity by presenting antigenic peptides to T lymphocytes, helping distinguish self from non-self. MHC molecules are divided into two classes: Class I, found on most nucleated cells, present endogenous (e.g., viral or tumor) peptides to CD8+ cytotoxic T cells; Class II, found on professional antigen-presenting cells, present exogenous (e.g., bacterial) peptides to CD4+ helper T cells. These interactions activate T cells & trigger immune responses.
๐น The MHC is remarkable for its extreme genetic polymorphism; the most variable region in the human genome with over 1,500 Class I & 1,000 Class II alleles. This diversity, driven by gene duplication, mutations, & gene conversion, enhances peptide-binding range across individuals.
๐น In organ transplantation, mismatched MHC alleles between donor & recipient can trigger immune-mediated rejection or GVHD. Accurate HLA typing significantly improves graft survival and patient outcomes. Furthermore, specific MHC alleles are strongly associated with autoimmune diseases. For instance, the allele HLA-B27 is linked to "ankylosing spondylitis", while variants of HLA-DR are associated with "rheumatoid arthritis" & "type 1 diabetes".
๐นCertain alleles confer protection or increased susceptibility to pathogens like "HIV", "hepatitis B", "tuberculosis", & "malaria ๐ฆ". These genetic associations have practical implications in designing vaccines & tailoring public health strategies for high-risk populations.
➡️ The MHC is central to immune recognition, linking antigen presentation to disease resistance, transplant compatibility, & immune regulation. Its genetic diversity drives individual differences in immune responses & supports defense against diverse pathogens. Ongoing research into its structure & function is enhancing advances in precision medicine, vaccines, & autoimmune therapies.
⚠️ In an Oystershell, the MHC stands as a testament to the intricate co-evolution of humans & their microbial environment, anchoring it as one of the most fascinating and clinically relevant gene families in human biology.
Abubakar Abubakar ✍๐ป
• Robinson, J., Halliwell, J. A., et alia.(2020). Nucleic Acids Research, 48(D1), D948–D955.
• Parham, P. (2021). The Immune System (5th ed.). Garland Science.
• Trowsdale, J., et al. (2013). Annual Review of Genomics & Human Genetics, 14, 301–323.
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