Granulocyte antigens play an important role in cell functions including adhesion, cell activation, and binding of immunoglobulins. The purpose of these studies is to better define the molecular basis of variations in neutrophil antigens and their role in neutrophil function. The Fc-gamma-receptor IIIb (Fc-gamma-RIIIB) genes that encode neutrophil-specific antigens NA1 and NA2 differ at five nucleotides, four that result in amino acid differences among the two alleles. We have described people with Fc-gamma-RIIIB genes that differ from the NA1-Fc-gamma-RIIIB and NA2-Fc-gamma-RIIIB by a single nucleotide have been described. We have also shown that these single nucleotide changes effect the expression of NA1 and NA2 antigens. Analysis of the granulocytes from people with variant NA genotypes revealed that single base substitutions in Fc-gamma-RIIIB at 141 and in Fc-gamma-RIIIB at 349 are important in the expression of NA1 and single base substitutions in Fc-gamma-RIIIB at 227 and 277 are important in the expression of the NA2. Recent studies have focused on granulocyte antign NB1 or CD177. The mRNA encoding CD177 has recently sequenced and it has been found to be highly homologous to a gene over expressed on granulocytes from people with polycythemia vera, polycythemia rubra vera gene-1 (PRV-1). We searched human genomic databases to determine the genomic structure of NB1. We only found one gene homogolous to CD177 and PRV-1 suggesting they are alleles of the same gene. However, the sequence of CD177 was incomplete. A sequence gap was present in this gene. The mRNA encoding CD177 has been cloned from a fetal liver cDNA libary and is being used to screen a human geneomic DNA libary. The CD177 gene will be sequenced and the molecular basis of antigen polymorphisms will be studied.
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