In 1994, a new set off loci related to MHC class 1 genes
called MHC class 1 chain-related genes (MIC) or Perth beta block transcript 11
were identified independently by Bahram et al. and Leelayuwat et al.in which
five copies existed. The nomenclature was then standardized as MIC, which since
then is in current use. Major
Histocompatibility complex class 1chain related molecule is known to play
an important role in tumor immune-surveillance.
MICA/B is encoded in the MHC (major histocompatibility
complex) region, and they share structural and sequence similarity with MHC
class I proteins (28-35%). MICA/B has α1-α2-α3 extracellular domains and short
transmembrane tails similar to MHC class 1. MICA/B does not associate with
β2-microglobulin or antigenic peptides like their counterpart MHC class 1. They
are highly polymorphic, with close to 60 recognizable MICA and 25 MICB alleles.
Although much is not known about the significance of their polymorphism, MICA
alleles might vary in their affinity for NKG2D binding and thus affect the
thresholds of recognition by NK cells and T lymphocytes.
The MIC molecules have been detected in broader range of
tumorshematological malignances and various adenocarcinomas such as breast,
lung, colon, kidney, ovary and prostate tumors, gliomas, neuroblastomas and
melanomas. Previous studies show that MIC genes are widely and transcribed and
therefore possibly translated and membrane bound with exception of the Central
Nervous system.
In human, NKG2D
recognizes two structurally distinct families of ligands namely (MIC)
molecules and the UL 16 binding proteins (ULBPs) 1-5 molecules which is also
known as RAET1: retinoic acid early transcript, originally identified through
interaction with Cytomegalovirus UL 16 glycoproteins. MIC and ULBP both engage
NKG2D, which then triggers cytokine production and cytotoxic activity seen in
activated NK cell.
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