Different stabilities of the structurally related receptors for IgE and IgG on the cell surface are determined by length of the stalk region in their alpha-chains
Kubota, T.; Mukai, K.; Minegishi, Y.; Karasuyama, H.
Journal of Immunology 176(11): 7008-7014
2006
ISSN/ISBN: 0022-1767 PMID: 16709862 Document Number: 600199
A variant of the high affinity IgE receptor Fc epsilon RI, which is composed of alpha- and gamma-chains without the beta-chain, is expressed on human APC, such as dendritic cells, and has been suggested to facilitate Ag uptake through IgE and hence to facilitate Ag presentation to T cells. The level of Fc epsilon RI on these cells is correlated with the serum IgE concentration, suggesting IgE mediates the up-regulation of the alpha gamma 2-type Fc epsilon RI. The IgE-mediated Fc epsilon RI up-regulation on mast cells and basophils has been shown to enhance the ability of these cells to release chemical mediators and cytokines that are responsible for allergic inflammatory reactions. Here, to elucidate the mechanism controlling Fc epsilon RI expression, we compared two structurally related Ig receptors, human Fc epsilon RI and Fc gamma RIIIA, which carry different a-chains but the same gamma-chains. The half-life of Fc epsilon RI on the cell surface was short unless it bound IgE, whereas Fc gamma RIIIA was stably expressed without IgG binding. Shuffling of the non Ig-binding portions of the Fc epsilon RI alpha and Fc gamma RHIII alpha chains revealed that the stalk region was critical in determining the difference in their stability and ligand-induced up-regulation. Unexpectedly, analyses with added or deleted amino acids in the stalk region strongly suggested that the length rather than the amino acid sequence of the stalk region was of major importance in determining the different stabilities of REM and Fc gamma RIIIA on the cell surface. This finding provides new insights into the mechanism regulating surface Fc epsilon RI expression.