Major�Histocompatibility�Complex

• Cluster of genes found in all mammals
• Its products play role in discriminating self/non-self
• Participant in both humoral and cell-mediated immunity
• MHC Act As Antigen Presenting Structures
• genes present within a long continuous stretch of DNA on chromosome 6 in humans and on chromosome 17 in mice.
• HLA complex in humans and as the H-2 complex in mice.

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Class I MHC

• genes encode glycoproteins expressed on the surface of nearly all nucleated cells;
• the major function of the class I gene products is presentation of peptide antigens to T_Ccells.

Class II MHC genes

• encode glycoproteins expressed primarily on antigen-presenting cells (macrophages, dendritic cells, and B cells),
• where they present processed antigenic peptides to T_Hcells.

Class III MHC genes

• encode, various secreted proteins that have immune functions,
• including components of the complement system and
• molecules involved in inflammation

The MHC Encodes Three Major Classes of Molecules

• Class I MHC molecules contain a 45-kilodalton (kDa) α chain associated non-covalently with a 12-kDa β₂-macroglobulin molecule.
• The α chain is a transmembrane glycoprotein encoded by polymorphic genes within the A, B, and C regions of the human HLA complex
• three external domains each containing approximately 90 amino acids; a transmembrane domain of about 25 hydrophobic amino acids

• Class II MHC molecules contain two different polypeptide
• chains, a 33-kDa α chain and a 28-kDa β chain, which associate by noncovalent interactions

• MHC Products Are Highly Polymorphic
• Vary considerably from person to person

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• However, Crossover Rate Is Low
• 0.5% crossover rate
• Inherited as 2 sets (one from father, one from mother)
• Haplotype refers to set from mother or father

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• MHC Alleles Are Co-dominantly Expressed
• Both mother and father alleles are expressed

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• Inbred Mice Haplotypes Are Designated With Italic Superscript
• Ex. H-2^b
• Designation refers to entire set of H-2 alleles