Human FcγRIIa (CD32a) contains a prevalent and clinically relevant polymorphism, possessing either a histidine (H) (CD32aH)- or arginine (R) (CD32aR) at amino acid position 131. Individuals expressing the CD32aH variant have higher risk of Crohn’s disease and ulcerative colitis through unknown mechanisms. We show that CD32aH binds IgG immune complexes (IC) more actively than its counterpart, CD32aR, especially in acidic environments typical of intracellular endosomes that process IC in antigen presenting cells (APC) for antigen presentation and downstream activation of T cells.