Altered I-A protein-mediated transmembrane signaling in B cells that express truncated I-Ak protein.
Recent evidence suggests that the major histocompatibility complex class II molecules of B lymphocytes function as signal-transducing receptors during the generation of T lymphocyte-dependent humoral immune responses. By analogy with other receptors, we postulate that perturbation of the class II molecules is coupled to the generation of intracellular second messengers through interactions involving the transmembrane and/or cytoplasmic domains of the class II molecules. We report a series of experiments that assess which amino acids of the class II molecule I-Ak are required for coupling it to the signal-transduction pathway. We prepared a series of B-lymphocyte transfectants that express I-Ak molecules with COOH-terminal truncations of either the Ak alpha or Ak beta chain or both. The ability of each transfected class II molecule to transduce a signal after being bound by monoclonal antibody was found by monitoring the translocation of protein kinase C from the cytosol to the "nuclear compartment" of the transfected B lymphocyte. Results indicate that the Ak beta chain plays the dominant role in signal transduction and that the 6 cytoplasmic amino acids of Ak beta chain most proximal to the inner plasma membrane are of greatest importance in coupling I-Ak molecules to the molecules of the signaling cascade.
Wade
W F
WF
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Chen
Z Z
ZZ
Maki
R
R
McKercher
S
S
Palmer
E
E
Cambier
J C
JC
Freed
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D003062:Codon / Q000235:genetics; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D003062:Codon; D000949:Histocompatibility Antigens Class II; D011493:Protein Kinase C