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Complement played a major role in augmenting the clearance and promoting hepatic sequestration of target erythrocytes in rats preinjected with IgG<jats:sub>2a<\/jats:sub> mAb directed against the S site. In contrast, an intact complement system was not an essential requirement for erythrocyte clearance when S site\u2010specific IgG<jats:sub>2b<\/jats:sub> mAb were used. With each antibody tested, (DA \u00d7 PVG)F<jats:sub>1<\/jats:sub> cells, expressing about half as much antigen, were removed significantly slower than DA erythrocytes, this finding being more pronounced when the animals had been preinjected with mAb of the IgG<jats:sub>2a<\/jats:sub> isotype. A comparison of the tissue distribution of DA and (DA \u00d7 PVG)F<jats:sub>1<\/jats:sub> erythrocytes indicated that hepatic uptake was greater for target cells expressing higher antigen density. A considerable degree of heterogeneity was observed in the <jats:italic>in vivo<\/jats:italic> behavior of the target erythrocytes with three groups of IgG<jats:sub>2b<\/jats:sub> mAb that recognized different sites on the class I molecule. The S site\u2010specific IgG<jats:sub>2b<\/jats:sub> mAb were much more efficient in the hepatic Fc receptor\u2010mediated clearance system than were the P site\u2010directed mAb of the same subclass. Our results suggest that antibody specificity may also be a contributory factor, in addition to antibody isotype and target cell antigen density, in determining the fate of target cells <jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/eji.1830210413","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T12:38:41Z","timestamp":1172752721000},"page":"943-950","source":"Crossref","is-referenced-by-count":10,"title":["Targeting behavior of rat monoclonal IgG antibodies <i>in vivo<\/i>: role of antibody isotype, specificity and the target cell antigen density"],"prefix":"10.1002","volume":"21","author":[{"given":"Nasim","family":"Yousaf","sequence":"first","affiliation":[]},{"given":"Jonathan C.","family":"Howard","sequence":"additional","affiliation":[]},{"given":"Bryan D.","family":"Williams","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,11,22]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"2650","volume":"42","author":"Levy R.","year":"1983","journal-title":"Fed. 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