The major histocompatibility complex (MHC) encodes molecules displayed on cell surfaces, where they participate in lymphocyte recognition and antigen presentation.

Left - click to enlarge - the presented antigen of the MHC-peptide complex is indicated by red. (Image source Molecule of Month: Illustration by David S. Goodsell of The Scripps Research Institute. Original work of the US Federal Government - public domain.)

The TCR and MHC-peptide complex make primary contact, then CD molecules bind to other portions of the MHC.

Almost ubiquitous, MHC class I interacts with TCRs and CD8 on cytotoxic T cells (CTCs, 'suppressor' T cells, regulator T cells). MHC class II is expressed primarily on cells that interact with pathogenic peptides. MHC II interacts with TCRs and with CD4 on helper T cells and cells that stimulate the immune system.

Proteins encoded by MHC genes identify the molecule as non-self or self. Non-self antigens – partly digested by lysosomes of leukocytes (monocytes or neutrophils) or displayed intact – are carried on the APC surface by class II histocompatibility molecules. Proteins of tumor cells or foreign invaders such as bacteria and viruses are carried by class I histocompatibility molecules. Non-self antigens provoke the immune response.

● Class I – encoded in BCA region – occur on almost every nucleated cell of the body, and are heterodimeric peptide binding proteins, antigen processing molecules such as TAP and Tapasin
● Class II – encoded in D region – occur only on specialized cell types, and are heterodimeric peptide binding proteins, proteins such as MHC II DM, MHC II DQ, and MHC II DP that that modulate peptide loading in the lysosomal compartment
● Class III – encoded between BCA and D regions – complement components such as C2, C4, factor B, and some that encode cytokines (e.g., TNF-α).

The Class I and Class II MHC molecules belong to molecules of the immunoglobulin supergene family, including immunoglobulins, T-cell receptors, CD4, and CD8. The major histocompatibility complex is encoded by several genes located on human chromosome 6 – class I molecules are encoded by the BCA region, while class II molecules are encoded by the D region. Sequences in the region between the BCA and D segments encodes class III molecules, which include some complement components and cytokines.

Human class II molecules are designated HLA-D, for human leukocyte antigen D, and the genes encoding them are also located in the major histocompatibility complex (MHC)

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