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The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8+ T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val). Therefore, this SNP has been investigated for associations with infections, autoimmune diseases, and cancer. Here, we systematically review these studies and analyze them in view of new data on the functional consequences of this polymorphism. It has been shown recently that the MICA-129Met variant elicits a stronger NKG2D signaling, resulting in more degranulation and IFN-γ production in NK cells and in a faster costimulation of CD8+ T cells than the MICA-129Val variant. However, the MICA-129Met isoform also downregulates NKG2D more efficiently than the MICA-129Val isoform. This downregulation impairs NKG2D-mediated functions at high expression intensities of the MICA-Met variant. These features of the MICA-129Met/Val dimorphism need to be considered when interpreting disease association studies. Particularly, in the field of hematopoietic stem cell transplantation, they help to explain the associations of the SNP with outcome including graft-versus-host disease and relapse of malignancy. Implications for future disease association studies of the MICA-129Met/Val dimorphism are discussed.
Pubmed ID: 28018354
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Database for sequences of the human major histocompatibility complex (HLA) and includes the official sequences for the WHO Nomenclature Committee For Factors of the HLA System. It currently contains 9,310 allele sequences (2013) along with detailed information concerning the material from which the sequence was derived and data on the validation of the sequences. It is established procedure for authors to submit the sequences directly to the IMGT/HLA Database for checking and assignment of an official name prior to publication, this avoids the problems associated with renaming published sequences and the confusion of multiple names for the same sequence. The need for reasonably rapid publication of new HLA allele sequences has necessitated an annual meeting of the WHO Nomenclature Committee for Factors of the HLA System. Additionally they now publish monthly HLA nomenclature updates both in journals and online to provide quick and easy access to new sequence information. The IMGT/HLA Database is part of the international ImMunoGeneTics project. In collaboration with the Imperial Cancer Research Fund (ICRF) and European Bioinformatics Institute (EBI) they have developed an Oracle database to house the HLA sequences in such a way as to allow users to present complex queries about the sequence, sequence features, references, contacts and allele designations to the database via a graphical user interface over the web. The IMGT/HLA Database Submission Tool allows direct submission of sequences to the WHO HLA Nomenclature Committee for Factors of the HLA System. The IMGT/HLA Database provides an FTP site for the retrieval of sequences in a number of pre-formatted files.
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