title: Gene required for normal MHC class II expression and function is localized to approximately 45 kb of DNA in the class II region of the MHC.
abstract: In certain mutant human B cell lines, MHC-encoded class II molecules displayed at the cell surface have an abnormal conformation and are unstable in the presence of SDS. The mutants cannot present exogenous protein Ags to T cells but elicit responses with exogenous antigenic peptides; thus, formation of intracellular complexes between antigenic peptides and class II molecules is impaired. Previous analysis of LCL deletion mutants, .82, .174, and 5.2.4, showed that genes needed for this function must be present in approximately 230 kb of DNA in the class II region of the MHC. We now describe a new deletion mutant, .61, which has normal class II-mediated Ag processing/presentation. The TAP1, TAP2, LMP2, and LMP7 genes are deleted from .61, demonstrating that those genes are not needed for normal formation of intracellular class II/peptide complexes. The genes in question must be located in DNA that is present in .61 and .82 (both normal) and absent from .174 and 5.2.4. (both defective). Mapping of the deletion breakpoints indicates that genes needed for normal class II-associated Ag processing/presentation are either: 1) in an approximately 40 kb L DNA segment located between the DMB and LMP2 loci or 2) in an R region between the DQA2 and DQB1 loci and are completely included on a 5.1-kb fragment formed by joining of DNA that flanks the deletion in .61. The evidence favors location of the genes in the L DNA segment.
authors.affiliation: Laboratory of Genetics, University of Wisconsin, Madison 53706.
authors.forename: S
authors.initials: S
authors.lastname: Ceman
authors.forename: J W
authors.initials: JW
authors.lastname: Petersen
authors.forename: V
authors.initials: V
authors.lastname: Pinet
authors.forename: R
authors.initials: R
authors.lastname: DeMars
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D026905:Amino Acid Transport Systems; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003546:Cysteine Endopeptidases; D004247:DNA / Q000032:analysis*; D005095:Exoribonucleases; D005656:Fungal Proteins / Q000235:genetics; D017353:Gene Deletion; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics; D006801:Humans; D009097:Multienzyme Complexes; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators / Q000235:genetics
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D026905:Amino Acid Transport Systems; D002352:Carrier Proteins; D005656:Fungal Proteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D009097:Multienzyme Complexes; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; D015534:Trans-Activators; C071313:LMP-2 protein; C071692:TAP2 protein, human; D004247:DNA; D005095:Exoribonucleases; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex