We investigated the lateral diffusion of the HIV receptor CD4 at the surface of T lymphocytes at 20 degrees C and 37 degrees C by Single Particle Tracking using Quantum Dots. We found that the receptors presented two major distinct behaviors that were not equally affected by temperature changes. About half of the receptors showed a random diffusion with a diffusion coefficient increasing upon raising the temperature. The other half of the receptors was permanently or transiently confined with unchanged dynamics on raising the temperature. These observations suggest that two distinct subpopulations of CD4 receptors with different environments are present at the surface of living T lymphocytes. (C) 2011 Elsevier Inc. All rights reserved.