T‐Lymphocyte Activation: The Biology and Function of CD2 and CD4

Bierer, Barbara E.; Burakoff, Steven J.

doi:10.1111/j.1600-065x.1989.tb00549.x

Cited by 84 publications

(41 citation statements)

References 86 publications

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“…The CD4 molecule could be involved as an adhesion molecule in CD3-or LFA-l-preactivated CD4+ Tcell adhesion. This is supported by the significant role of CD4 in antigen-specific T cell adhesion [27,28]. Similarly, it has been recently shown that in a long-term (1 to 2,5 h) adhesion assay TcR triggering could up-regulate the CD8-MHC class I interac tion [29].…”

Section: Discussionmentioning

confidence: 78%

Regulation of LFA‐1‐mediated T cell adhesion by CD4

et al. 1991

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Heterotypic adhesion of T lymphocytes to monocytes, B lymphocytes, or other target cells is mainly mediated by LFA-1 and CD 2 molecules. Low-affinity binding of restingTcells can be transiently up-regulated by cross-linking of CD3. We have previously found that binding of specific ligands to CD4 can down-regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross-linking using plastic-bound anti-CD3 antibody can also be inhibited by several CD4 ligands, i.e. anti-CD4 antibodies, the gpl60 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp 160-binding site to CD4 (positions 418-434 and 449-464) and a 12-mer synthetic peptide (DR-12) analogous to positions 35-46 of HLA class II |3 subunit and including the highly conserved Arg-Phe-Asp-Ser (RFDS) sequence» After CD3 cross-linking, maximal binding of Tcells to HLA class II-positive and -negative B cells was similar, although binding to HLA class II-negative B cells was more prolonged.Tcells that were passively induced to up-regulate adhesion by binding of a CD 1 la-specific antibody, NKIL16, known to enhance LFA-1-dependent adhesiveness, were less sensitive to the inhibitory effect of the DR-12 peptide, whereas the inhibitory effects of gpl60 were preserved. The kinetics of adhesion of NKIL16-pretreated T cells was not influenced by LILA class II expression at the B cell surface. Together, these results strongly suggest that CD4-HLA class II interaction may down-regulate low-affinity adhesion of resting T cells and, to some extent, high-affinity adhesion of T cells actively induced by CD3 cross-linking but not passively induced by an anti-CD 11a antibody 1 Introduction

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Section: Discussionmentioning

confidence: 78%

Regulation of LFA‐1‐mediated T cell adhesion by CD4

et al. 1991

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“…The primary signal is initiated through the interaction of the antigen-major histocompatibility complex on antigen-presenting cells (APCs) with the T cell receptor (TCR) [5,6]. The secondary or costimulatory signal is provided by a co-receptor-ligand interaction [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…T cell activation is a two-signal process requiring antigenspecific [5,6] and costimulatory signals [7]. The primary signal is initiated through the interaction of the antigen-major histocompatibility complex on antigen-presenting cells (APCs) with the T cell receptor (TCR) [5,6].…”

Section: Introductionmentioning

confidence: 99%

Transferrin receptor in T cell activation and transplantation

Bayer

Baliga

Woodward

1998

Journal of Leukocyte Biology

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Transferrin receptor (TfR) expression is up-regulated during T cell activation after the interaction of the T cell receptor with the antigenmajor histocompatibility complex and the expression of interleukin-2 (IL-2) receptor. We hypothesize that anti-TfR monoclonal antibody (mAb) will prolong allograft survival by altering T cell responses. In a murine heterotopic nonvascularized cardiac allograft model, CBA/J (H-2 k ) recipients were transplanted with neonatal C57BL/6 (H-2 b ) donor hearts. Anti-TfR or isotype-matched control mAbs (100 g) were administered at the time of transplantation and on the following day. Splenocytes from naive CBA/J mice were stimulated in vitro with C57BL/6 alloantigen. Anti-TfR mAb was administered at 5 g/mL during the initiation of culture. Cytotoxic T lymphocyte (CTL) and mixed lymphocyte responses (MLR) were performed to assess T cell function. After 24 h in culture, cells were harvested, RNA isolated, and semi-quantitative reverse transcriptase-polymerase chain reaction performed. Anti-TfR mAb prolonged allograft survival to 25.7 ؎ 0.9 days compared to the isotype control (10.7 ؎ 0.4 days, P F 0.01, Wilcoxon rank sum). Anti-TfR mAb completely abrogated the CTL response and suppressed the MLR by 70-86% compared to the isotype controls. Anti-TfR mAb suppressed IL-2, interferon-␥ (IFN-␥), IL-10, and IL-12 p40 mRNA expression, but had no effect on IL-4, IL-12 p35, and IL-15 mRNA expression. In conclusion, anti-TfR mAb prolongs allograft survival, suppresses T cell function, and alters IL-2, IL-10, IL-12 p40, and IFN-␥ mRNA expression. These data suggest that the downregulation in IL-12 mRNA by anti-TfR mAb may prevent the development of T helper cells, thereby promoting graft survival and altering cell-mediated immune responses. The partial effect by anti-TfR mAb on cytokine mRNA expression may be due to other contributing factors such as costimulation.

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“…W hile the TCR confers recognition of peptide antigens in the context of MHC proteins, several other T cell proteins contribute to T function by transducing biochemical signals or by augmenting cellular adhesion (1). CD2 is a T cell glycoprotein that plays a dual role in T cell activation.…”

mentioning

confidence: 99%

“…T cell activation is triggered by certain pairs of mAb directed against different CD2 epitopes (3), and the interaction of CD58 with CD2 enhances antigen-specific T activation (4). CD2 and CDlla/CD18 (LFA-1) provide the T cell with two pathways for regulating cellular adhesion (1,5). Occupancy of the TCP, has been shown to upregulate the avidity of both CD2 (6) and LFA-1 (7) for their respective ligands, albeit through distinct signaling pathways (7,8).…”

mentioning

confidence: 99%

Separable portions of the CD2 cytoplasmic domain involved in signaling and ligand avidity regulation.

Hahn

Bierer

1993

The Journal of Experimental Medicine

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SummaryEffective T cell immune responses require the molecular interplay between adhesive and signaling events mediated by the T cell receptor for antigen (TCR) and other cell surface coreceptor molecules. In this report, we have distinguished between the role of regulated adhesion and transmembrane signaling in coreceptor function using the T cell glycoprotein CD2. By binding its ligands on antigen-presenting cell (APC), CD2 serves both to initiate signal transduction events and to promote cellular adhesion. Furthermore, the avidity of CD2 for one ligand, CD58 (LFA-3), is regulated by TCR signaling. We have expressed wild type CD2 and a series of mutated CD2 molecules in an antigen-specific murine T cell hybridoma. Structure-function studies using these stably transfected cell lines identify two structurally and functionally distinct regions of the 116 amino acid (aa) cytoplasmic domain. One region is required for CD2-mediated signal transduction, and a separate COOH-terminal 21 aa portion is required for CD2 activity regulation. Cell lines expressing CD2 molecules lacking the cytoplasmic segment required for CD2-initiated IL-2 production retain the ability to upregulate CD2 avidity. Conversely, cell lines expressing CD2 mutants lacking the cytoplasmic segment required for avidity regulation retain the ability to initiate CD2-specific signaling. In antigen-specific T cell responses, basal binding of CD2 to its ligands enhances antigen responsiveness only minimally, whereas regulated avidity and transmembrane signaling are both required for optimal coreceptor function. Taken together, these studies demonstrate the independent contributions of regulated adhesion and intracellular signaling in CD2 coreceptor function.W hile the TCR confers recognition of peptide antigens in the context of MHC proteins, several other T cell proteins contribute to T function by transducing biochemical signals or by augmenting cellular adhesion (1). CD2 is a T cell glycoprotein that plays a dual role in T cell activation. Through interactions with its ligands CD58 (LFA-3), CD59, and CD48 (reviewed in reference 2), CD2 initiates intracellular signaling cascades and enhances intercellular adhesion to APC. T cell activation is triggered by certain pairs of mAb directed against different CD2 epitopes (3), and the interaction of CD58 with CD2 enhances antigen-specific T activation (4). CD2 and CDlla/CD18 (LFA-1) provide the T cell with two pathways for regulating cellular adhesion (1, 5). Occupancy of the TCP, has been shown to upregulate the avidity of both CD2 (6) and LFA-1 (7) for their respective ligands, albeit through distinct signaling pathways (7,8).Although the importance of signaling and adhesion is well established, the relative contributions of these processes to T cell coreceptor function and antigen responsiveness have been difficult to assess. Here we have used CD2 as a model system to dissect these functions. Expression of human wild type and mutant CD2 molecules in an antigen-specific murine T cell hybridoma has permitted...

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T‐Lymphocyte Activation: The Biology and Function of CD2 and CD4

Cited by 84 publications

References 86 publications

Regulation of LFA‐1‐mediated T cell adhesion by CD4

Regulation of LFA‐1‐mediated T cell adhesion by CD4

Transferrin receptor in T cell activation and transplantation

Separable portions of the CD2 cytoplasmic domain involved in signaling and ligand avidity regulation.

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