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Acoustic biosensors are sensitive not only to mass coupling but also to visco-elastic changes occurring close to the sensor surface. In this work, a surface acoustic wave (SAW) device, operating at 110 MHz and with a penetration depth of ~100 nm, has been applied to monitor the binding between membrane-bound proteins (HLA-A2) and surface-immobilized antibodies (anti-HLA-A2). The sensitivity of amplitude change correlated to the number of HLA-A2/antibody complexes formed on the device surface. This allowed for the calculation of the two-dimensional (2D) kinetics and affinity constant of the HLA-A2/antibody interaction based on real-time acoustic data.