S. Ceman et al., DMA AND DMB ARE THE ONLY GENES IN THE CLASS-II REGION OF THE HUMAN MHC NEEDED FOR CLASS II-ASSOCIATED ANTIGEN-PROCESSING, The Journal of immunology, 154(6), 1995, pp. 2545-2556
Previous studies have shown that homozygous mutations between the LMP2
and DNA loci in the human MHC cause class II molecules to be abnormal
ly conformed and unstable in the presence of SDS at low temperature, a
nd impede class II-associated Ag processing and presentation. These ab
normalities result from impaired ability to form intracellular class I
I/peptide complexes that predominate in normal cells. We show in this
work that this defect results from deficient expression of either the
DMA or the DMB gene. Human B-LCL.174 (DR3) cells, which have a deletio
n of all known expressible genes in the class II region, express trans
gene-encoded HLA-DR3, but have the abnormalities. Transfer of cosmid H
A14, which contains the DMA and DMB genes, into.174 (DR3) cells restor
ed normal DR3 conformation, stability in 0.4% SDS at 0 degrees, and ab
ility to process and present tetanus toroid, but only when both DMA an
d DMB mRNAs were present. The requirement for both genetic expressions
in engendering normal phenotypes was confirmed by transferring the cl
oned genes into.174 (DR3) cells separately or together. Because normal
phenotypes were fully restored in transferent cells expressing DMA pl
us DMB, other genes in the similar to 1-mb homozygous class II region
deletion in.174 (DR3) cells either do not participate in or are dispen
sable for apparently normal production of intracellular class II/pepti
de complexes. The properties of DM-deficient EBV-transformed B lymphob
lastoid cell lines (LCLs) suggest ways of identifying humans in whom D
M deficiency contributes to congenital immunodeficiency and malignancy
.