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The role of the interaction of CD2 molecules with lymphocyte function-associated antigen 3 (LFA-3) in facilitating nominal antigen recognition by T lymphocytes was studied by utilizing an HLA-DR4-restricted CD4+ cytotoxic human T-cell clone specific for human immunodeficiency virus envelope glycoprotein gpl20 as a responder and murine flbroblasts transfected with human class II major histocompatibility complex (MHC) and/or human LFA-3 molecules as antigenpresenting cells (APC). Although expression of the DR4 restriction element in fibroblasts is sufficient for T-cell recognition of a gpl20 peptide as judged by induction of proliferation, coexpression of human LFA-3 on DR4+ APC decreases the molar requirement of nominal antigen by greater than one order ofmagnitude. Both LFA-3 and the relevant class H MHC molecules are necessary for antigen-independent conjugate formation, but the binding is further enhanced by specific nominal antigen. CD2-LFA-3 interaction is independent of T-cell receptor-MHC interaction and contributes directly to the stabilized conjugate between the T cell and LFA-3-bearing APC; soluble CD2 and monoclonal antibodies to LFA-3 and CD2 reduce T-cell-APC binding to the level mediated by nominal antigen and MHC. During conjugate formation, CD2 but not CD3 molecules are reorganized into the cell-cell interaction site in an antigen-independent manner. Thus, reorganization and/or coassociation of CD2 with CD3 molecules is not essential for T-cell activation.The ability ofT lymphocytes to recognize specific antigens in the context of class I and class II major histocompatibility complex (MHC) molecules is determined by the unique clonotypic T-cell receptor (TCR)-CD3 complex which they individually bear. The process of antigen recognition involves the physical interaction of a TCR with a nominal peptide antigen bound to a specific MHC molecule referred to as a restricting element. This process is not singularly dictated by the TCR complex itself, but rather is dependent on other structures, including CD4, CD8, CD2, and lymphocyte function-associated antigen 1 (LFA-1) (reviewed in refs. 1-3). CD4 and CD8 structures bind to monomorphic regions of class II and class I MHC structures, respectively, thereby facilitating the interaction of the TCR with the MHC restricting element (reviewed in ref. 4). In addition to the MHC binding accessory structures, a set of adhesion structures facilitates non-antigen-specific interactions between T lymphocytes and their cognate partners. This set includes the CD2/lymphocyte function-associated antigen 3 (LFA-3) receptor-ligand pair (5, 6).Studies employing antibodies directed against CD2 or LFA-3 as well as murine T-cell hybridoma transfectants expressing human CD2 have suggested that CD2-LFA-3 interaction is important for the T-cell recognition process (7,8). However, virtually nothing is known about the mechanism by which CD2-LFA-3 interaction augments T-cell recognition-in particular, whether the interaction influences recognition of nominal antigen and whet...

Introduction:Evidence strongly suggests that soluble oligomers of amyloid beta protein (oAβ) help initiate the pathogenic cascade of Alzheimer's disease (AD). To date, there have been no validated assays specific for detecting and quantifying oAβ in human blood. Methods:We developed an ultrasensitive oAβ immunoassay using a novel capture antibody (71A1) with N-terminal antibody 3D6 for detection that specifically quantifies soluble oAβ in the human brain, cerebrospinal fluid (CSF), and plasma.Results: Two new antibodies (71A1; 1G5) are oAβ-selective, label Aβ plaques in nonfixed AD brain sections, and potently neutralize the synaptotoxicity of AD brainderived oAβ. The 71A1/3D6 assay showed excellent dilution linearity in CSF and plasma without matrix effects, good spike recovery, and specific immunodepletion. Discussion:We have created a sensitive, high throughput, and inexpensive method to quantify synaptotoxic oAβ in human plasma for analyzing large cohorts of aged and AD subjects to assess the dynamics of this key pathogenic species and response to therapy.

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The HIV envelope glycoprotein gp120 binds with high affinity to CD4 and is responsible for the tropism of HIV for CD4+ T cells and monocytes. Efforts to develop HIV vaccines have focused on gp120 and, therefore, a detailed molecular understanding of human immune responses to gp120 is essential. In this report, we have used human T cell clones specific for gp120 to examine the processing and presentation of gp120 to T cells. In particular, we examined the role of the CD4 that is expressed at low levels on the surfaces of human monocytes in the presentation of gp120 by monocytes. The presentation of gp120 to gp120-specific human T cell clones was blocked by pretreatment of monocytes with anti-CD4 mAb. Blocking of monocyte CD4 with anti-CD4 did not inhibit presentation of other Ag or of synthetic peptides representing epitopes within gp120 recognized by gp120-specific T cell clones. These results indicated that the anti-CD4-mediated inhibition occurred at the level of the monocyte, was specific for the gp120 response, and was operative at the initial Ag uptake phase of the Ag-processing pathway. Definitive confirmation that monocyte CD4 functions in the initial uptake step of the gp120-processing pathway was obtained by using soluble CD4 to block the interaction of gp120 with monocyte CD4. These results demonstrate that gp120 expressed by human monocytes plays an important role in the initial uptake of gp120 by monocytes and that gp120 taken up via CD4 is subsequently processed to allow for exposure of epitopes recognized by gp120-specific human T cells. At limiting gp120 concentrations, uptake via CD4 is essential for the presentation of gp120.