Antigen presentation abrogated in cells expressing truncated Ia molecules.
Oligonucleotide site-directed mutagenesis was used to introduce a premature stop codon in wildtype A beta k and A alpha k cDNA clones to create truncated A beta k and A alpha k molecules lacking the cytoplasmic domain. Transfected B lymphoma cells expressing an I-Ak molecule with a truncated beta-chain or with truncated alpha- and beta-chains showed profound defects in two Ia-related functions: Ia-restricted Ag presentation and intracytoplasmic signaling. The ability of these transfected cell lines to activate autoreactive T hybrids was markedly impaired whereas loss of Ag presentation to nominal Ag-specific T hybrids was more subtle. Ia-mediated transmembrane signaling as measured by PKC translocation from cytosol to nucleus after stimulation with anti-Ak antibody was greatly affected by truncation of the A beta and A alpha cytoplasmic domains. These results indicate an important role for the highly conserved cytoplasmic domain in Ia-mediated responses.
Nabavi
N
N
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115.
Ghogawala
Z
Z
Myer
A
A
Griffith
I J
IJ
Wade
W F
WF
Chen
Z Z
ZZ
McKean
D J
DJ
Glimcher
L H
LH
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002467:Cell Nucleus / Q000201:enzymology; D003001:Cloning, Molecular / Q000379:methods; D003600:Cytosol / Q000201:enzymology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000302:isolation & purification; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011493:Protein Kinase C