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To study the interaction of the TCR with its ligand, the complex of a MHC molecule and an antigenic peptide, we modified a TCR contact residue of a H-2K d -restricted antigenic peptide with photoreactive 4-azidobenzoic acid. The photoreactive group was a critical component of the epitope recognized by CTL clones derived from mice immunized with such a peptide derivative. The majority of these...
Circulating lymphocytes home to the mucosal lymphoid organs, Payees patches (PP), through high endothelial venules (HEV). In situ analyses revealed that transfused lymph node cells (LNCs) interact with PP-HEV in a series of overlapping adhesion events: L-selectin (CD62L) >α4β7 initiates Interaction, L-selectin and α4β7 both participate In rolling, and Gαi-linked activation triggers arrest that...
We previously identified an HLA-B8 + donor, NW, whose lymphoblestoid cells failed to present a B8-restricted epitope from the influenza A nucleoprotein following viral infection, although added peptide could still be presented. The failure to present through HLA-B8 following viral infection appears to be specific for the NP epitope. Here, we report that donor NW makes an HLA-132702-restricted...
T cell activation through the TCR can result in either cell proliferation or cell death. The role of costimulatory receptors i n regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 costimulation to augment the production of IL-2, which...
Pathogenic self-reactive antibodies are a significant cause of morbidity and mortality and contribute to both cytotoxic and Immune complex-triggered Inflammatory disorders, typified by rheumatic diseases, autoimmune hemolytic anemia, and thrombocytopenla. Roles have been proposed for Fc receptors, complement, and complement receptors in the pathogenesis of these disorders, although the contribution...
Cytokine and cytokine receptor gene knockout mice provide powerful experimental systems to characterize the functions of these molecules in resistance to infectious disease. Such mice may also provide unique models of immune deficiency to learn whether manipulation of the Immune response can overcome the specific dysfunction. We demonstrate that resistance of IFNγ gene knockout (GKO −/− )...
CD19-deficient mice were generated to examine the role of CD19 in B cell growth regulation In vivo. Deletion of CD19 had no deleterious effects on the generation of B cells in the bone marrow, but there was a significant reduction in the number of B cells in peripheral lymphoid tissues. B cells from CD19-deficient mice exhibited markedly decreased proliferative responses to mitogens, and serum Immunoglobulin...
The propagation of mouse mammary tumor virus (MMTV) has been analyzed in mice defective for expnasion of CD40 ligand (CD40L). Mice with endogenous viral superantigen (SAG) delete T cells with cognate Vβ independent of CD40L expression. Nevertheless, CD40L − mice do not show deletion of cognate T cells after being exposed to infectious MMTV and have greatly diminished viral replication. The...
An immature v-abl-transformed mast cell line (V3-MC) was derived from a mouse that developed systemic mastocytosis after transplantation of v-sbl-infected bone marrow cells. V3-MCs injected intravenously into adult BALE/c mice infiltrated the liver, spleen, and intestine by day 6 and underwent progressive differentiation and maturation, eventually resembling indigenous mast cells. In terms of their...
Calcium and calcium-binding proteins play important roles in the signaling cascade leading from the initial engagement of TCRs on T cells to the fully activated state. To undertake a molecular dissection of this cascade, we first isolated a Jurkat T cell line derivative containing the NF-AT promoter element driving transcription of the diphtheria toxin A chain gene (dipA), resulting in rapid cell...
Flavivirus infection of mammalian cells increases the cell surface expression of major histocompatibility complex (MHC) class I molecules, the recognition elements for cytotoxic T cells. Here, we show that the mechanism for flavivirus-induced up-regulation of class I MHC involves an increase in peptide supply to the endoplasmic reticulum. Flavivirus-mediated peptide supply for MHC class I assembly...
We studied the extent of functional linkage between CD3ζ and p56 lck In pre-TCR-dependent thymocyte development. Differentiation of DN to DP cells was examined by treatment of RAG2/CD3ζ and RA G1/p56 lck double-deficient mice with anti-CD3ζ antibodies. The results suggest that CD3ζ has no specific role in this maturation step, but may be important for amplification of signaling through...
Major histocompatibility complex (MHC) class II molecules bind antigenic peptides rapidly after biosynthesis in antigen-presenting cells (APCs). By contrast, the rate of peptide binding to purified class II molecules is remarkably slow. We find that purified HLA-DR molecules bind peptides rapidly in the presence but not the absence of HLA-DM, a recently identified heterodlmer required for efficient...
The Ets and AP-1 families of transcription factors bind distinct DNA elements and subserve diverse functions in multiple lymphoid and nonlymphoid cell types. Functionally important Ets and AP-1 binding sites have been identified in a large number of enhancer elements, suggesting Important cooperative interactions between these two families of transcription factors. In this report, we have demonstrated...
We used surface plasmon resonance to study the binding of a set of soluble mouse I-E class II major histocompatibility molecules, each occupied by a different single peptide, to the staphylococcal enterotoxin superantigens, SEA and SEB. The rates of association and dissociation to SEA varied greatly depending on the I-E-bound peptide. By contrast, binding to SEB yielded fast association and dissociation...
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