MHC/HLA: GENETICS OF IMMUNE RECOGNITION

"𝕋𝕙𝕖 𝕄ℍℂ 𝕤𝕪𝕤𝕥𝕖𝕞 𝕣𝕖𝕡𝕣𝕖𝕤𝕖𝕟𝕥𝕤 𝕠𝕟𝕖 𝕠𝕗 𝕥𝕙𝕖 𝕞𝕠𝕤𝕥 𝕡𝕠𝕝𝕪𝕞𝕠𝕣𝕡𝕙𝕚𝕔 𝕘𝕖𝕟𝕖 𝕗𝕒𝕞𝕚𝕝𝕚𝕖𝕤, 𝕖𝕤𝕤𝕖𝕟𝕥𝕚𝕒𝕝 𝕚𝕟 𝕚𝕞𝕞𝕦𝕟𝕚𝕥𝕪 𝕒𝕟𝕕 𝕥𝕣𝕒𝕟𝕤𝕡𝕝𝕒𝕟𝕥𝕒𝕥𝕚𝕠𝕟."  Dr. Anthony Fauci

          🧬 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.

           🔹 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. 

          🔹 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".

          🔹Certain alleles confer protection or increased susceptibility to pathogens like "HIV", "hepatitis B", "tuberculosis", & "malaria 🦟". 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 ✍🏻

• 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.

#MHC #InfectiousDiseases #TCells #HLAAlleles #MedicalResearch #Vaccine #Immunogenetics #CRISPR #PublicHealth⚕️