MHC and Related Structures

Brief Introduction of MHC and Related Structures

MHC (major histocompatibility complex) is a cluster of genes arranged in a long sequence of DNA sequences on human chromosome 6, which encodes MHC molecules. MHC molecules are cell surface glycoprotein receptors that play an important role in recognizing foreign substances as antigen-presenting structures. There are two main classes of MHC molecules: class I and class II. Class I MHC molecules are expressed on the surface of all nucleated cells and platelets. They are required for presenting peptide antigens to cytotoxic T cells. Class II MHC molecules are primarily found on antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B-cells. They present peptide antigens to helper T cells, which stimulate an immune reaction from other cells. Besides, there are also some MHC-related structures or molecules involved in the recognition by T cells, such as MICA and MICB (MHC class I chain-related, A and B) as well as endothelial protein C receptor (EPCR).

Role of MHC and Related Structures in Tumor

MICA and MICB molecules are regarded as markers of cellular distress and can be induced by cellular stress, damage, or transformation. MICA and MICB proteins are ligands for NKG2D found on most NK cells, some CD8 T cells, and certain populations of γδ T cells such as Vγ9Vδ2 T cells. The interaction of the ligands MICA and MICB with their corresponding receptors NKG2D triggers cytotoxic effector activity of natural killer cells and certain T-cell subsets and promotes cytokine production. Owing to the NKG2D mediated cytotoxicity of Vγ9Vδ2 T cells, they appear to be a promising tool for novel immunotherapies against many types of tumors. In addition to MICA and MICB proteins, the EPCR, an MHC-like molecule, is also a ligand of γδ TCR. A study showed human γδ TCR could directly bind EPCR, thus making γδ T cells recognize endothelial cells which are targets for cytomegalovirus infection and epithelial tumors.

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Fig.1 NKG2D ligands and HCMV. (Cerwenka, 2001)

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Reference

1. Cerwenka, A.; Lanier, L.L. Natural killer cells, viruses and cancer. Nature Reviews Immunology. 2001, 1: 41-49.