Previously, we described conserved protein clusters including MHC I and II glycoproteins, ICAM-1 adhesion molecules, and interleukin-2 and -15 receptors in lipid rafts of several human cell types. Differential protein-protein interactions can modulate function, thus influence cell fate. Therefore, we analyzed supramolecular clusters of CD4(+) T cells from draining lymph nodes and peripheral blood of colorectal carcinoma patients, and compared these to healthy controls. Superclusters of MHC I and II with IL-2/15 receptors were identified by confocal microscopy on all cell types. Flow-cytometric FRET revealed molecular associations of these proteins with each other and with ICAM-1 as well. In draining lymph nodes expression levels of all these proteins were lower, and interactions, particularly between IL-2/15 receptors and MHC molecules weakened or disappeared as compared to the control. Stimuli/local conditions can rearrange cell surface protein patterns on the same cell type in the same patient, having important implications on further function and cell fate.