Search for adenosine A(2A) spare receptors on peripheral human lymphocytes

Some ligand–receptor couples involve spare receptors, which are apparent when a maximal response is achieved with only a small fraction of the receptor population occupied. This situation favours cross-reactions with low-affinity ligands, which may be detrimental for cell signaling. In the case of the adenosine A(2A) receptors (A(2A)R), which have an immunosuppressive effect on lymphocytes through cAMP production, the presence of spare A(2A)R remains to be established. We examined the situation using patients over-expressing lymphocyte A(2A)R and an agonist-like mAb to A(2A)R. We found that maximal mAb binding and functional response varied among the patients whereas the dissociation constant and half-maximal effective concentration had similar mean values (0.19 and 0.18 μM, respectively). Lymphocyte A(2A)R expression was correlated to plasma adenosine level and A(2A)R occupation but not to A(2A)R response. These results are consistent with a lack of a reserve of functional A(2A)R on human lymphocytes as a general rule and suggest that the amount and functional state of the expressed A(2A)R determine the maximal level of the lymphocyte response to adenosine.