Population study of allelic diversity in the human MHC class I-related MIC-A gene.
The polymorphism of major histocompatibility complex (MHC) class I HLA-A, -B, and -C molecules may have evolved through pathogen-driven selection of alleles with diverse peptide-binding specificities. Two MHC-encoded molecules that are distantly related to class I, MIC-A and MIC-B, do not function in the presentation of pathogen-derived peptides to T cells with alphabeta T-cell receptors (TCRs), but are broadly recognized by intraepithelial T cells with gammadelta TCRs. However, both MIC-A and MIC-B are polymorphic, displaying an unusual distribution of a number of variant amino acids in their extracellular alpha1, alpha2, and alpha3 domains. In order to further define the polymorphism of MIC-A, we examined its alleles among 275 individuals with common and rare HLA genotypes. Of 16 previously defined alleles, 12 were confirmed and 5 new alleles were identified. A two-by-two analysis of MIC-A and HLA-B alleles uncovered a number of statistically significant associations. These results confirm and extend previous knowledge on the polymorphism of MIC-A. The strong positive linkage of certain MIC-A and HLA-B alleles may have implications for studies related to MHC-associated diseases and transplantation.
Petersdorf
E W
EW
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, Seattle, WA 98109-1024, USA. epetersd@fhcrc.org
Shuler
K B
KB
Longton
G M
GM
Spies
T
T
Hansen
J A
JA
D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary; D005787:Gene Frequency; D014644:Genetic Variation; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen