MIC-A polymorphism in Japanese and a MIC-A-MIC-B null haplotype

A polymorphic gene, MIG-A, is one of the MIC family of genes which is composed of a group of homologous genes interspersed in the class III and class I regions of the major histocompatibility complex. MIG-A is located 46 kilobases (kb) centromeric of HLA-B, and is preferentially expressed in the epithelial cells and intestinal mucosa. Recently, MIG-A and the closely related MIC-B were reported as the molecules that conferred specificity in the recognition by the V delta 1 gamma delta T cells. In the present study, polymorphic exons 2, 3, and 4 of the MIG-A gene were analyzed using the polymerase chain reaction-single-strand conformation polymorphism method. The number of patterns found in exons 2, 3, and 4 were 5, 6, and 4, respectively, in 114 healthy Japanese subjects. Eight MIG-A alleles were observed in Japanese individuals, among which one, tentatively named MIC-AMW, has not previously been reported. There was a strong linkage disequilibrium between MIG-A and HLA-B loci: each MIG-A allele showed strong association with a particular HLA-B group. In contrast, B*3901 showed association with multiple MIG-A alleles. Furthermore, the existence of a MIC-A-MIC-B null haplotype, which is associated with HLA-B*4801, was identified. In this haplotype, a large-scale deletion (of approximately 100 kb) including the entire MIG-A gene was indicated and the MIC-B gene possessed a stop codon.