Abstract
Immunoglobulin E (IgE) is a central mediator of immediate-type hypersensitivity reactions. Our laboratory previously discovered that the membrane-bound IgE (mIgE) on human B cells contains an extra peptide segment of 52 amino acid residues, referred to as C(epsilon)mX, between the CH4 domain and the membrane-anchor peptide. The sequence of C(epsilon)mX is unique in the entire protein bank. While the function and possible roles of C(epsilon)mX in the regulation of IgE production remain unknown, C(epsilon)mX has provided as a potential site for immunological targeting of IgE-expressing B cells for the treatment of allergic diseases. In the present study, we analyze the C(epsilon)mX in human and several non-human primates, as a way to understand the function of C(epsilon)mX. We have cloned the C(epsilon)mX segment in genomic DNA (gDNA) and cDNA from chimpanzee, gorilla, orangutan, gibbon, olive baboon and Formosan macaque, using PCR and primers designed from the sequences of human C(epsilon)mX and its neighboring segments. Between human and the above listed six non-human primate species, the C(epsilon)mX share homology of 98.51 %, 100 %, 93.28 %, 88.06 %, 85.07 % and 85.07 % in amino acid sequences, respectively. Sequencing data showed that in addition to some variations within the C(epsilon)mX segment, there are also variations in the adjacent extracellular segment, referred as migis-epsilon, of the membrane-anchor peptide. These variations include Gly21Glu, Gly31Arg, Ser33Pro, His36Asp, Pro37His, Arg38His, His40Arg, Pro51Leu, Val56Leu, Gly63Ser, Ala65Val and Pro66Leu (between human and Formosan macaque). We are in progress studying 20 individuals of Formosan macaque to analyze potential allotypic variations in C(epsilon)mX and migis-epsilon. The information on the genetic variation among human and non-human species may help us understand the function and structure of those segments and their roles in the regulation of IgE. The results may also be used to evaluate the suitability of using certain non-human primate species, such as Formosan macaque, as an animal model for studying the therapeutic targeting of IgE-expressing B cells using immunological agents that aim at C(epsilon)mX.