A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC

It is becoming increasingly apparent that many of the genes in the class II I region of the human MHC encode proteins involved in the immune and inflam matory responses. Furthermore, genetic studies have indicated that genes wi thin the class III region, particularly the telomeric segment containing th e TNF gene, could contribute to susceptibility to diseases of immune-relate d etioloy. We have sequenced an 82-kb segment of DNA around the TNF gene to identify candidate disease susceptibility genes in this region. The 10 kno wn genes in this region have been precisely positioned with the order allog raft inflammatory factor I, G1, 1C7, leukocyte-specific transcript 1 (B144) , lymphotoxin B, TNF, lymphotoxin ii, NB6, IKBL, BAT1 (centromere to telome re), and their genomic structures have been defined. Comparison of the Gf g enomic region with previously described cDNA and genomic sequences, togethe r with the results of reverse transcriptase PCR, indicates that three alter native transcripts, G1, allograft in flammatory factor 1, and IFN-gamma-res ponsive transcript, are all derived from this gene. The completion of the s equence of 1C7 (D6S2570) has revealed that this gene encodes a putative nov el member of the Ig superfamily, A number of alternatively spliced transcri pts of 1C7 were identified by reverse transcriptase-PCR, all of which are e xpressed in immune-related cell lines. Alternative splicing within the Ig d omain-encoding region was seen to result in possible set switching between an IgV domain and an IgC2 domain. Lastly, a previously unidentified gene, h omologous to a number of V-ATPase G subunits, has been located 1 kb telomer ic of IKBL.