TY - JOUR
T1 - The cytoplasmic and the transmembrane domains are not sufficient for class I MHC signal transduction
AU - Gur, Hanan
AU - Geppert, Thomas D.
AU - Wacholtz, Mary C.
AU - Lipsky, Peter E.
N1 - Funding Information:
1This work was supported by NIH Grants AR09989, AR36169, and AR38319. 2To whom correspondence should be addressed at present address: Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel 52621. Fax: 972-35302011. H.G. is a recipient of the Wasserman and the Harris Awards of the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - Class I MHC molecules deliver activation signals to T cells. To analyze the role of the cytoplasmic and the transmembrane (TM) domains of class I MHC molecules in T cell activation, Jurkat cells were transfected with genes for truncated class I MHC molecules which had only four intracytoplasmic amino acids and no potential phosphorylation sites or native molecules or both. Cross-linking either the native or the truncated molecules induced IL-2 production even under limiting stimulation conditions of low engagement of the stimulating mAb. Moreover, direct comparison of transfected truncated and native class I MHC molecules expressed on the same cell revealed significant stimulation induced by cross-linking the truncated molecules, despite low expression. In addition, truncated class I MHC molecules were as able to synergize with CD3, CD2, or CD28 initiated IL-2 production as native molecules. In further experiments, hybrid constructs made of the extracellular portion of the murine CD8 α chain and of the TM and the intracytoplasmic domains of H-2K(k) class I MHC molecule were transfected into Jurkat T cells. The expression of the transfected hybrid molecules was comparable to that of the native HLA-B7 molecules. Cross-linking the intact monomorphic HLA-A,B,C epitope or the polymorphic HLA-B7 epitope induced IL-2 production upon costimulation with PMA. In contrast, cross-linking the hybrid molecules generated neither an increase in intracellular calcium concentration ([Ca2+](i) nor stimulated IL.2 production. By contrast, cross-linking intact murine class I MHC molecules induced [Ca2+](i), signal and IL-2 production in transfected Jurkat cells. The data therefore indicate that unlike many other signaling molecules, signaling via class I MHC molecules does not involve the cytoplasmic and the TM portions of the molecule, but rather class I MHC signal transduction is likely to be mediated by the extracellular domain of the molecule.
AB - Class I MHC molecules deliver activation signals to T cells. To analyze the role of the cytoplasmic and the transmembrane (TM) domains of class I MHC molecules in T cell activation, Jurkat cells were transfected with genes for truncated class I MHC molecules which had only four intracytoplasmic amino acids and no potential phosphorylation sites or native molecules or both. Cross-linking either the native or the truncated molecules induced IL-2 production even under limiting stimulation conditions of low engagement of the stimulating mAb. Moreover, direct comparison of transfected truncated and native class I MHC molecules expressed on the same cell revealed significant stimulation induced by cross-linking the truncated molecules, despite low expression. In addition, truncated class I MHC molecules were as able to synergize with CD3, CD2, or CD28 initiated IL-2 production as native molecules. In further experiments, hybrid constructs made of the extracellular portion of the murine CD8 α chain and of the TM and the intracytoplasmic domains of H-2K(k) class I MHC molecule were transfected into Jurkat T cells. The expression of the transfected hybrid molecules was comparable to that of the native HLA-B7 molecules. Cross-linking the intact monomorphic HLA-A,B,C epitope or the polymorphic HLA-B7 epitope induced IL-2 production upon costimulation with PMA. In contrast, cross-linking the hybrid molecules generated neither an increase in intracellular calcium concentration ([Ca2+](i) nor stimulated IL.2 production. By contrast, cross-linking intact murine class I MHC molecules induced [Ca2+](i), signal and IL-2 production in transfected Jurkat cells. The data therefore indicate that unlike many other signaling molecules, signaling via class I MHC molecules does not involve the cytoplasmic and the TM portions of the molecule, but rather class I MHC signal transduction is likely to be mediated by the extracellular domain of the molecule.
UR - http://www.scopus.com/inward/record.url?scp=0033082699&partnerID=8YFLogxK
U2 - 10.1006/cimm.1998.1417
DO - 10.1006/cimm.1998.1417
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0033082699
VL - 191
SP - 105
EP - 116
JO - Cellular Immunology
JF - Cellular Immunology
SN - 0008-8749
IS - 2
ER -