Class II antigen processing defects in two H2d mouse cell lines are caused by point mutations in the H2-DMa gene.
The molecular nature of the defect in two mouse antigen processing-defective cell lines was examined. Both mutants were derived from the A20 (BALB/c, H2d) B cell line, and both were found to have defects in the H2-DMa gene. Mutant 3A5 exhibits severely reduced amounts of H2-DMa message, and no detectable DMalpha protein. cDNA sequence revealed a C-->T transition at nucleotide 118, introducing a premature stop codon in exon 2 of the H2-DMa gene. In contrast, mutant 2A2 exhibits reduced but detectable levels of H2-DMa message and DMalpha protein only after treatment with IL-4, which induces the expression of both the H2-DMa and the H2-DMb genes in B cells. In this mutant the cDNA sequence revealed a missense mutation in exon 3 resulting in the conversion of a conserved proline residue in the Ig-like domain to serine. Stable transfection with full-length H2-DMa cDNA reconstitutes the antigen processing capacity of both mutants, as demonstrated by the ability to present native antigen to T cell clones, and by restored class II SDS stability.
Russell
H I
HI
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, OH 45267-0524, USA.
York
I A
IA
Rock
K L
KL
Monaco
J J
JJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000235:genetics* / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017354:Point Mutation; D012333:RNA, Messenger; D011817:Rabbits; D014162:Transfection
D006183:H-2 Antigens; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger