Length and sequence requirements of the cytoplasmic domain of the A beta molecule for class II-mediated B cell signaling.
APC use class II molecules of the MHC to present peptide Ag to Th cells. Interaction of the TCR and CD4 with the class II-peptide complex, together with co-stimulatory signals provided by the APC, activates the T cell. B lymphocytes express class II molecules and can also be induced to express co-stimulatory molecules, allowing them to act as APC to Th cells. In addition to T cell activation, class II binding by T cells has been shown to result in the transmission of signals to B cells. Signal transduction via MHC class II has been well documented in B cells of both mice and humans and is implicated in the processes of cellular adhesion, Ag presentation, and Ag-dependent B cell activation. The regions of the class II MHC molecule which are involved in signal transduction to the B cell are not clearly defined. However, previous studies have suggested that the beta chain of the alpha beta heterodimer has a predominant role in B cell signaling. To examine the role of the cytoplasmic domain of this molecule in class II-mediated signaling to a mouse B cell clone, we have prepared and analyzed a set of subclones expressing sequentially truncated forms of A beta b. Our results demonstrate that only the 8 membrane-proximal amino acids of the cytoplasmic domain are required for signaling. However, specific conserved amino acids within this minimal length are required for successful signal transduction; length alone is not sufficient. Examination of the signaling ability of these truncated beta chains suggests that conserved residues at positions 227 and 228 of the cytoplasmic domain may have particularly important effects on signal transduction. A beta b chains from which the entire cytoplasmic domain have been removed are still capable of transmitting a detectable, although reduced, signal to B cells. Thus, the transmembrane and/or extracellular domains may also be involved in the signaling process.
Harton
J A
JA
Department of Microbiology, University of Iowa, Iowa City 52242.
Bishop
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D002999:Clone Cells; D003593:Cytoplasm / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D000949:Histocompatibility Antigens Class II