Characterization and genomic mapping of a novel leader peptide associated with the human VH4-21 (VH4-34) gene segment

The human IgVH locus is located on chromosome 14, band q32 and spans approximately 1 mb. Within this locus are approximately 120 VH gene segments that are subdivided into six to seven families based on sequence homology of their coding regions. VH4-21 (VH4-34) is a member of the VH4 family, a family that contains 10 to 15 members. It is expressed in a variety of circumstances including early fetal development, the autoantibody repertoire, and in a highly restricted manner in antibodies that recognize alloantigens on the surface of human red blood cells. Most interesting, however, is the expression of this gene segment in T cells as a semi-germline transcript in conjunction with a nontraditional VH leader peptide. This nonhydrophobic leader sequence, termed "Et" for exon in T cells, has previously been shown to reside within the VH locus. Using YAC and P1 clones, we have identified two copies of this exon, both of which are located in the region of the locus that contains VH4-24 (VH4-34). Characterization of the two exons suggests that they arose by duplication, as flanking DNA is almost identical over a distance of > 5 kb. Preliminary data suggests they are both located > 20 kb upstream of VH4-21 (VH4-34).