ANALYSIS OF HLA-DMB MUTANTS AND HLA-DMB GENOMIC STRUCTURE

The HLA-DM locus encodes class II-like A and B chains and apparently r egulates the antigen presentation function of conventional major histo compatibility complex (MHC) class II molecules. Here we describe the H LA-DMB mutations in three presentation defective B lymphoblastoid cell s lines (B-LCL), 7.19.6, 10.6.6, and 10.78.6, which express DMB transc ripts of abnormal length. Mutant 7.19.6 has a C --> T point mutation t hat introduces a 5' splice site into exon 3 of DMB. The independently derived mutants, 10.6.6 and 10.78.6, each harbor a G --> A mutation in exon 3 and also lack an identical downstream segment of RNA. Mapping of DMB intron/exon borders, using a genomic clone, revealed that the s egment missing in mutants 10.6.6 and 10.78.6 represents the fourth exo n of DMB; no mutations were found within exon 4 in either 10.6.6 or 10 .78.6, however. In addition, the DMB gene was found to have a six exon genomic structure, typical of MHC class II B genes.