Influence of Fc gamma-receptor polymorphisms on efficacy of antibody-mediated lymphocyte depletion in rhesus macaques

The in vivo application of monoclonal antibodies (mAbs) in nonhuman primates has enhanced our understanding of correlates of immune protection. However, the in vivo efficacy of mAbs in nonhuman primates is variable. Investigations in humans treated with mAbs have shown that functional variability may depend, at least in part, on polymorphisms of Fcgreceptors.We investigated polymorphisms of FcγRI, FcγRIIA, FcγRIIB, and FcγRIIIA by sequencing of cDNA in rhesus monkeys (RM) treated with different lymphocyte-depleting mAbs (anti-CD20, anti-CD8, or anti-CD4). Eighty-nine rhesus monkeys treated with anti-CD20 (Rituximab), anti-CD8 (cM-T807), anti-CD4 (OKT4a), or control antibody were examined. Animals were bred and housed at different primate centers; therefore, they represent a heterogeneous pool of unrelated animals. Depending on the duration of lymphocyte depletion, animals were stratified …