Allelic repertoire of the human MHC class I MICA gene

Abstract

The hallmark of the classical major histocompatibility complex (MHC) class I molecules is their astonishing level of polymorphism, a characteristic not shared by the nonclassical MHC class I genes. A distinct family of MHC class I genes has been recently identified within the human MHC class I region. The MICA (MHC class I chain-related A) gene in this family is a highly divergent member of the MHC class I family and has a unique pattern of tissue expression. We have sequenced exons encoding the extracellular alpha1, alpha2, and alpha3 domains of the MICA gene from twenty HLA homozygous typing cell lines and four unrelated individuals. We report the identification of eleven new alleles defined by a total of twenty-two amino acid substitutions. Thus, the total number of MICA alleles is sixteen. Interestingly, a tentative superimposition of MICA variable residues on the HLA-A2 structure reveals a unique pattern of distribution, concentrated primarily on the outer edge of the MICA putative antigen binding cleft, apparently bordering an invariant ligand binding site.

Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

“…26,27 The sequences and the transmembrane microsatellite length were analyzed using SeqScape v2.6 and GeneMapper v4.0 software (ThermoFisher Scientific), respectively. Final MICA genotypes were assigned using an in-house-developed software that compiled sequence data and transmembrane genotypes.…”

MICA intron 1 sequences of conserved extended HLA haplotypes: implications for sequencing-based typing

“…This new primer (5 0 -CAC CTG TGA TTT CCT CTT CCC CAG AGC) corresponds to sequence lying between nucleotide positions 6926 and 6952 in the reference MICA sequence (GI:1405892). The exon 2 forward primers used by others 2,17,18 are also outside the polymorphic region in intron 1.…”

“…Methods for genotyping include PCR-SSP, SSOP, RSCA, [10][11][12][13][14][15] along with sequencing-based typing (SBT) usually considered definitive. 2,[16][17][18][19] Results have differed for the same reference cell lines typed by alternative methods. As examples, the cell line WJR076 was typed as *017 by SBT 2 and PCR-SSP, 12 but also reported as *031.…”

“…1 The MICA (MHC class I chain-related gene A) (MICA; Locus ID: 4276) gene is highly polymorphic and has a unique pattern of tissue expression. 2,3 Although MICA protein is MHC class I related, it does not associate with beta-2-microglobulin; it may function as a stress-induced antigen that is broadly recognized by intestinal epithelial gd T cells and as a ligand for cells expressing the activating natural killer-cell receptor NKG2D. 3 The involvement of MICA molecules in tumor immunology and in the immune response to viral infections and to allografts has recently been suggested.…”

Takayasu Arteritis. Insights into Immunopathology.

“…55,56) Up to now, at least 16 alleles of MICA have been identified. 57) As for the polymorphism of the MICA gene (triplet repeat in the transmembrane region), a strong association of 6 GCT repetitions with Behcet disease was reported.…”