MHC class I polypeptide-related sequence B (MIC-B, MICB, PERB112)
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Function
- seems to have no role in antigen presentation
- acts as a stress-induced self-antigen that is recognized by gamma delta T cells
- ligand for the KLRK1/NKG2D receptor
- binding to KLRK1 leads to cell lysis
- unlike classical MHC class I molecules, does not form a heterodimer with beta-2-microglobulin
- binds as a monomer to a KLRK1/NKG2D homodimer
- KLRK1 forms a complex with HCST/DAP10 in which KLRK1 binds MICB while HCST acts as an adapter molecule which enables signal transduction
- receptor-ligand interaction induces clustering of both proteins in ordered structures called immune synapses & also leads to their intercellular transfer; this is associated with a reduction in the cytotoxicity of KLRK1-expressing cells
Structure
- belongs to the MHC class I family, MIC subfamily
- contains 1 Ig-like C1-type (immunoglobulin-like)
Compartment
- cell membrane
- binding to human cytomegalovirus glycoprotein UL16 causes sequestration in the endoplasmic reticulum
Alternative splicing
named isoforms=3
Expression
- widely expressed with the exception of the central nervous system where it is absent
- induced by heat shock, oxidative stress, retinoic acid, IFN-alpha & the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine.
Pathology
- expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate & colon
- in hepatocellular carcinomas, expressed in tumor cells but not in surrounding non-cancerous tissue
- proteolytically cleaved & released from the cell surface of tumor cells
- the MICA*004 allele is associated with susceptibility to rheumatoid arthritis
- binds to human cytomegalovirus glycoprotein UL16 which causes sequestration of MICB in the endoplasmic reticulum & increases resistance to KLRK1-mediated cytotoxicity
- genetic variation in MICB is associated with cytomegalovirus & herpes simplex virus I seropositivity & this may be associated with schizophrenia risk
- induction by IFN-alpha is impaired in patients with chronic hepatitis C virus infection
- down-regulated by human cytomegalovirus UL112 microRNA during viral infection which leads to decreased binding of KLRK1/NKG2D & reduced killing by natural killer cells
Polymorphism
- the following alleles of MICB are known: MICB*001, MICB*002, MICB*003, MICB*004, MICB*005, MICB*006, MICB*007, MICB*008, MICB*009N, MICB*010, MICB*011, MICB*012, MICB*013, MICB*014, MICB*015, MICB*016, MICB*018, MICB*019, MICB*020, MICB*021N & MICB*022
- MICB*009N & MICB*021N are null alleles which are not expressed
- the sequence shown is that of MICB*001
Notes
- GC to AG nucleotide substitution in intron 1 generates a splice junction which gives rise to an additional exon between exons 1 & 2
- may be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay