Lower left quadrant: unstained cells, lower right: CD32AR-Ig bound EA, upper left: CD32AH-Ig bound EA, upper right: EA bound to both the CD32A-Ig molecules. CD32ARhas significantly lower affinity towards all three subtypes as compared to CD32AH. Our data suggest that the lower binding of CD32ARnot only to IgG2 but also to IgG1 and IgG3 might be responsible for the lack of clearance of IC leading to increased susceptibility to bacterial infections and autoimmune diseases. Our data further suggests that in humans, inflammatory cells from CD32AR/Hheterozygous individuals may predominantly use the H allele to mediate antibody coated target cell binding during phagocytosis and ADCC, resulting in a phenotype similar to CD32AHhomozygous individuals. == INTRODUCTION == Of the receptors for the Fc domain of immune-complexes (IC), the low affinity Fc gamma receptors (FcR) play a central role in many types of antibody-dependent cellular cytotoxicity (ADCC) and immunophagocytosis (15). In Capromorelin humans, CD32A, the type II FcR, is the major phagocytic Fc receptor (6). Human CD32A has low Capromorelin affinity for monomeric IgG, but it binds stably to immune-complexes. CD32A has been shown to exhibit a polymorphism in the ligand-binding domain. This single nucleotide polymorphism in the ligand binding domain causes a substitution of amino acid arginine (CD32AR) to histidine (CD32AH) at position 131. Both CD32A alleles binds to human IgG1 and IgG3, but the CD32ARallotype shows a lower binding for human IgG2 when compared to CD32AH(79). Evidences Capromorelin suggest that CD32ARallele is associated with increased susceptibility to bacterial infections (1015). Human IgG2 is the major subclass of antibody elicited by encapsulated bacteria in humans including human pathogens such asNeisseria meningitidis,Haemophilus influenzaeandStreptococcus pneumoniae(1618). Arthur et al. (19) showed that 90% of CD32ARhomozygous individuals are more susceptible toS. pneumococcalinfection. Apart from bacterial infections, CD32ARallele is also associated with susceptibility to the development of certain autoimmune disease such as systemic lupus erythematosus (SLE) (16,2024). Various clinical studies have shown that SLE patients who are CD32ARhave a higher likelihood of developing proteinurea, hemolytic anemia, antinuclear RNP antibodies, glomerulonephritis and hypocomplementenia (25). Development of SLE at a younger age was reported in patients with the CD32ARgenotype, with an earlier incidence of arthritis, sicca syndrome, nephritis, lymphadenitis, hemotologic abnormalities, lupus anticoagulant, cryoglobulinemia and hypocomplementemia (25). Taken together, these studies suggest that the CD32A polymorphism plays a pivotal role in certain infectious and autoimmune diseases. The increased susceptibility of Capromorelin CD32ARhomozygous individuals for the observed diseases may be due ITGAV to the poor clearance of IC. Homozygous CD32AHindividuals, in contrast, are not susceptible to certain bacterial infections and autoimmune diseases because ICs are cleared efficiently (20,21,26,27). Interestingly, CD32AR/Hheterozygous individuals are also resistant to certain bacterial infections even though they express the CD32ARallele. It is not clear why the coexpression of CD32ARin heterozygous individuals is not reducing the efficiency of CD32AHallele. We hypothesize that in heterozygous individuals, CD32AHoutcompetes CD32ARfor ligand binding when both alleles are expressed on the same cell. To test our hypothesis, Capromorelin we have analyzed the interaction of immune-complexes with cells expressing R and H allelic forms of CD32A and their competition for ligand binding using recombinant dimeric forms of soluble R and H forms of CD32A alleles. The results presented here demonstrate that CD32AHoutcompetes CD32ARwhen they simultaneously compete for the same ligand. Such a dominance of CD32AHallele in heterozygous individuals may be due to the higher affinity of CD32AHfor all human IgG isotypes as compared to CD32ARwhich is demonstrated herein by cell binding assays and 2D affinity measurement studies. == MATERIALS AND METHODS == == Cell lines and Reagents.