Major histocompatibility complex class I chain-related gene A (MICA) was identified within the human leukocyte antigen (HLA) class I region and was located 46 kb centromeric from HLA-B locus. It functions as a ligand for human gammadelta T, CD8 T and natural killer (NK) cells by binding the NKG2D receptor. The aims of the present study were to determine the distribution of MICA alleles and MICA-HLA-B haplotypes in a sample of Euro-Brazilians. Through the combination of three typing methods, polymerase chain reaction (PCR)-sequence-specific oligonucleotide probe, PCR-sequence-specific primer and PCR-restriction fragment length polymorphism, 19 alleles were detected besides a MICA gene deletion in a sample composed by 204 unrelated Euro-Brazilians. The most commonly observed alleles were: MICA*00801 (25.3%), MICA*00201 (17.7%) and MICA*00901 (13.7%). The GCT repeat polymorphism variant A6 was the most commonly found. The most frequent haplotype found in this study was MICA*00901-B*51 (8.1%), followed by haplotypes MICA*00201-B*35 (6.1%) and MICA*00801-B*07 (6.1%). MICA*00801 truncated product, and its low affinity for NKG2D receptor may work as an inhibitor in its putative soluble form. It may also be that selective forces may favor MICA*00801 heterozygosity with NKG2D high affinity MICA alleles enabling activation and inhibition of cytotoxic activity of cells expressing the NKG2D receptor. The possibility of selective neutrality or of balancing selection still provides no explanation for MICA gene polymorphisms. Is it maintained by genetic drift or by the influence of migratory waves? Are there favored alleles while others present the same adaptive value?

A project of the 15th International Histocompatibility Workshop examined the rarity of human leukocyte antigen (HLA) alleles. A section was constructed in the website, www.allelefrequencies.net to contain this data from different sources. A mechanism to search the data was implemented for use by any individual.

MICA is a nonclassical polymorphic MHC molecule. We investigated MICA allelic frequencies and MICA-HLA-B-HLA-C haplotypes in Brazilian Amerindians to describe the polymorphism and to extract information about the evolution of MICA gene. Kaingang is the first population described to have a high frequency of MICA*020, found associated with HLA-B*3505-HLACw*0401. Allele MICA*020 probably originated de novo in South America. The Guarani population had high frequencies of MICA*027. Allele MICA*00801 is common worldwide but rare among Amerindians, occurring only because of gene flow. The analysis of the 64 described MICA alleles revealed that in exons 2 and 4, synonymous substitutions are in excess, a result compatible with purifying selection. The opposite was observed for exons 3 and 6 and the excess of nonsynonymous substitutions was significant for exon 3, indicating positive selection. Few of the alleles described so far had exon 6 sequenced, impeding conclusions for the corresponding portion of the molecule. The analysis of the entire gene is required for a better understanding of the evolution of MICA's polymorphism and its functional consequences. This knowledge is of prime importance in view of the increasing awareness of the functional and medical implications of MICA gene variability.

A high proportion of human recurrent spontaneous abortions (RSA) remain unexplained. The possible association between RSA and different genetic polymorphisms within the human leucocyte antigen system (HLA system, the human major histocompatibility complex) has been investigated with conflicting results since many decades. Here, we describe a case-control study with 136 Southern Brazilian women of predominantly European ancestry (75 control and 61 cases with unexplained RSA). We investigated the relationship between unexplained RSA and alleles and genotypes from two classical loci of the HLA: HLA-DRB1 and HLA-DQB1, as well as three loci related to cytokine production and their serum levels: TNFA (-308G>A), IL10 (-1082G>A, -819T>C, -592A>C) and IFNG (+874A>T). Genotyping was performed by an allele-specific PCR method. While all results concerning cytokine-related genes turned out to be negative, we found the genotype HLA-DQB1*02:02, 03:01 to be significantly decreased and the allele HLA-DRB1*11:04 to be significantly increased among patients.

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