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

In certain mutant human B cell lines, MHC-encoded class II molecules d isplayed at the cell surface have an abnormal conformation and are uns table in the presence of SDS. The mutants cannot present exogenous pro tein Ags to T cells but elicit responses with exogenous antigenic pept ides; thus, formation of intracellular complexes between antigenic pep tides and class II molecules is impaired. Previous analysis of LCL del etion mutants, .82, .174, and 5.2.4, showed that genes needed for this function must be present in approximate to 230 kb of DNA in the class II region of the MHC. We now describe a new deletion mutant, .61, whi ch has normal class II-mediated Ag processing/presentation. The TAP1, TAP2, LMP2, and LMP7 genes are deleted from .61, demonstrating that th ose genes are not needed for normal formation of intracellular class I I/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 tha t genes needed for normal class II-associated Ag processing/presentati on are either: 1) in an approximate to 40 kb L DNA segment located bet ween the DMB and LMP2 loci or 2) in an R region between the DQA2 and D QB1 loci and are completely included on a 5.1-kb fragment formed by jo ining of DNA that flanks the deletion in .61. The evidence favors loca tion of the genes in the L DNA segment.