Many Immunity-Related Genes Populate the MHC Locus in Human and Mouse Genomes

The major histocompatibility complex (MHC), also known as the human leukocyte antigen (HLA) complex in humans and H2 complex in mice, is a highly polymorphic genomic region responsible for encoding proteins crucial for immune responses. The organization of the MHC locus differs slightly between mice and humans, but both contain class I, class II, and class III regions.

In Humans (HLA Complex):

1. Class I Region (HLA-A, HLA-B, HLA-C):
   • Encodes classical class I molecules such as HLA-A, HLA-B, and HLA-C.
   • These molecules present endogenous peptides to CD8+ T cells, playing a crucial role in cytotoxic T cell-mediated immunity.
   • Also includes non-classical class I genes such as HLA-E, HLA-F, and HLA-G, which have specialized functions in immune regulation.
2. Class II Region (HLA-DP, HLA-DQ, HLA-DR):
   • Encodes classical class II molecules such as HLA-DP, HLA-DQ, and HLA-DR.
   • These molecules present exogenous peptides to CD4+ T cells, initiating helper T cell-mediated immune responses.
   • Also contains genes encoding the invariant chain (Ii) and the class II-associated invariant chain peptide (CLIP), involved in the assembly and trafficking of class II molecules.
3. Class III Region:
   • Contains genes with diverse functions, including those involved in complement activation, inflammation, and antigen presentation regulation.
   • Includes genes such as complement components (C2, C4, factor B), tumor necrosis factors (TNF-α, TNF-β), heat shock proteins, and others.
   • Not directly involved in antigen presentation but plays important roles in immune regulation and inflammation.

In Mice (H2 Complex):

1. Class I Region (H2-K, H2-D, H2-L):
   • Encodes classical class I molecules such as H2-K, H2-D, and H2-L.
   • Similar to humans, these molecules present endogenous peptides to CD8+ T cells.
   • Also includes non-classical class I genes with specialized immune functions.
2. Class II Region (H2-A):
   • Encodes classical class II molecules such as H2-Aα and H2-Aβ chains.
   • These molecules present exogenous peptides to CD4+ T cells, similar to human class II molecules.
   • Additionally, contains genes encoding the invariant chain and associated proteins involved in class II antigen presentation.
3. Class III Region:
   • Contains genes with diverse functions, including those involved in complement activation, inflammation, and immune regulation.
   • Similar to humans, includes genes encoding complement components, tumor necrosis factors, and other immune-related proteins.

In both humans and mice, the MHC locus is highly polymorphic, with numerous allelic variants present within each gene, contributing to the diversity of immune responses and individual susceptibility to diseases.

Next Topic: MHC Class I and II Protein Structure and Function

Source: ChatGPT response prompted and edited by Joel Graff.

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