Human lymphocyte function associated antigen-1 (LFA-1): identification of multiple antigenic epitopes and their relationship to CTL-mediated cytotoxicity.

Human lymphocyte function-associated antigen (LFA)-1, a heterodimeric lymphocyte surface glycoprotein of 177,000 and 95,000 relative molecular weight has been implicated to function in the cytotoxic T lymphocyte (CTL) effector mechanism. Seven mouse hybridoma lines producing monoclonal antibodies (MAb) reactive with this structure were studied. Three unique and 3 partially over-lapping epitopes on human LFA-1 were defined by competitive cross inhibition binding assays using biosynthetically labeled anti-LFA-1 MAb. In contrast, of five rat antimouse LFA-1 MAb, all five recognized a common or shared epitope. An HLA-B7 specific human CTL line expressed 1.1 X 10(5) LFA-1 sites per cell with a direct saturation binding assay. Human CTL expressed two to four times more LFA-1 than peripheral blood lymphocytes or B and T lymphoblastoid cell lines. Titration of each of the anti-LFA-1 MAb in a 51chromium release cytolytic assay revealed quantitative differences in the ability of the different anti-LFA-1 MAb to block cytolysis indicating distinct functional and antigenic epitopes exist on the human LFA-1 molecule. Anti-LFA-1 MAb reversibly inhibited the CTL reaction by slowing the initial rate of cytolysis. These results suggest anti-LFA-1 MAb inhibit CTL function by specific blockade of a functionally relevant molecule.

• Publication year

  1983

• Venue

  Journal of Immunology

• Publication date

  1983-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/jimmunol.131.3.1182PMID 6193178
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Molecular Interactions in T‐Cell‐Mediated Cytotoxicity

  1983cited by this paper
• Simultaneous flow cytometric analysis of human T cell activation antigen expression and DNA content

  1983cited by this paper
• Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3.

  1982cited by this paper
• Cloned T Lymphocytes and Monoclonal Antibodies as Probes for Cell Surface Molecules Active in T Cell‐Mediated Cytolysis

  1982cited by this paper
• Monoclonal antibodies reacting with immunogenic mycoplasma proteins present in human hematopoietic cell lines.

  1982cited by this paper
• Selective inhibition of human T cell cytotoxicity at levels of target recognition or initiation of lysis by monoclonal OKT3 and Leu-2a antibodies

  1982cited by this paper
• Human cytotoxic T cell structures associated with expression of cytolysis. I. Analysis at the clonal cell level of the cytolysis‐inhibiting effect of 7 monoclonal antibodies

  1982cited by this paper
• Monomorphic anti-HLA-A,B,C monoclonal antibodies detecting molecular subunits and combinatorial determinants.

  1982cited by this paper
• Inhibition of murine T cell‐mediated cytolysis and T cell proliferation by a rat monoclonal antibody immunoprecipitating two lymphoid cell surface polypeptides of 94000 and 180000 molecular weight

  1982cited by this paper
• LFA‐1 and Lyt‐2,3, Molecules Associated with T Lymphocyte‐Mediated Killing; and Mac‐1, an LFA‐1 Homologue Associated with Complement Receptor Function 1

  1982cited by this paper
• Lymphoid Cell Surface Interaction Structures Detected Using Cytolysis‐Inhibiting Monoclonal Antibodies

  1982cited by this paper
• High molecular weight lymphocyte surface proteins are structurally related and are expressed on different cell populations at different times during lymphocyte maturation and differentiation.

  1982cited by this paper
• Surface structures involved in target recognition by human cytotoxic T lymphocytes.

  1982cited by this paper
• Specificity of OKT4+ cytotoxic T lymphocyte clones.

  1982cited by this paper
• Molecular interactions in human T cell-mediated cytotoxicity to EBV II. Monoclonal antibody OKT3 inhibits a post-killer-target recognition/adhesion step.

  1982cited by this paper
• Antibody directed at a surface structure inhibits cytolytic but not suppressor function of human T lymphocytes

  1981cited by this paper
• Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells?

  1981cited by this paper
• Flow cytometric estimation of DNA and RNA content in intact cells stained with Hoechst 33342 and pyronin Y.

  1981cited by this paper
• Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.

  1981cited by this paper
• Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.

  1981cited by this paper
• T cell growth factor receptors. Quantitation, specificity, and biological relevance

  1981cited by this paper
• Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing.

  1981cited by this paper
• Use of Monoclonal Anti-mouse Immunoglobulin to Detect Mouse Antibodies

  1981cited by this paper
• Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man

  1981cited by this paper
• A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure.

  1981cited by this paper
• Studies on the induction and expression of T cell-mediated immunity. XII. The concomitant loss and recovery of membrane-associated Lyt-2 antigens, lymphocyte-target cell binding, and the antigen-specific and -nonspecific cytotoxic activity of alloimmune T lymphocytes after treatment with trypsin.

  1981cited by this paper
• A monoclonal antibody blocking human T cell function

  1980cited by this paper
• IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement.

  1980cited by this paper
• Interaction of cytotoxic T lymphocytes and target cells.

  1980cited by this paper
• Blocking effect of lyt-2 antibodies on T cell functions

  1980cited by this paper
• C1q: isolation from human serum in high yield by affinity chromatography and development of a highly sensitive hemolytic assay.

  1979cited by this paper
• Cytotoxic T cells: Lyt phenotype and blocking of killing activity by Lyt antisera.

  1979cited by this paper
• Monoclonal Antibodies for Analysis of the HLA System

  1979cited by this paper
• Mouse alloantibodies capable of blocking cytotoxic T-cell function. I. Relationship between the antigen reactive with blocking antibodies and the Lyt-2 locus

  1979cited by this paper
• Isolation of pure IgG1, IgG2a and IgG2b immunoglobulins from mouse serum using protein A-sepharose.

  1978cited by this paper
• Monoclonal antibody to a human histocompatibility alloantigen, HLA-A2

  1978cited by this paper
• Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens

  1978cited by this paper
• Surface-specific iodination of membrane proteins of viruses and eucaryotic cells using 1,3,4,6-tetrachloro-3alpha,6alpha-diphenylglycoluril.

  1978cited by this paper
• Enhanced autoradiographic detection of 32P and 125I using intensifying screens and hypersensitized film

  1977cited by this paper
• Mechanism of specific tumor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaction.

  1977cited by this paper
• T-Cell-mediated cytolysis: an overview of some current issues.

  1977cited by this paper
• Enhanced representation of HL-A antigens on human lymphocytes after mitogenesis induced by phytohemagglutinin or Epstein-Barr virus.

  1975cited by this paper
• Antigens on mouse and rat lymphocytes recognized by rabbit antiserum against rat brain: The quantitative analysis of a xenogeneic antiserum

  1975cited by this paper
• Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A.

  1975cited by this paper
• A simplified method for cyanogen bromide activation of agarose for affinity chromatography.

  1974cited by this paper
• Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

  1970cited by this paper

• The effects of polymer-mediated immunocamouflage on allorecognition of blood cells

  2014cites this paper
• Simultaneous Perturbation of CD154 and Transplantation Tolerance Induced by CD4-Dependent Generation of Dominant

  2013cites this paper
• platelets Expression of the leukocyte functional molecule (LFA-1) on mouse

  2011cites this paper
• An Animal Model

  2005cites this paper
• Small molecule LFA-1 antagonists compete with an anti-LFA-1 monoclonal antibody for binding to the CD11a I domain: development of a flow-cytometry-based receptor occupancy assay.

  2003cites this paper
• LFA-1 Pathways Simultaneous Perturbation of CD 154 and Transplantation Tolerance Induced by CD 4-Dependent Generation of Dominant Gelhaus

  2002cites this paper
• CD4-Dependent Generation of Dominant Transplantation Tolerance Induced by Simultaneous Perturbation of CD154 and LFA-1 Pathways1

  2002cites this paper
• Interferon-gamma is not a universal requirement for islet allograft survival.

  2002cites this paper
• ICAM-1 ( CD 54 ) : A Counter-Receptor for Mac-1 ( CDllb / CD 18 )

  2002cites this paper
• The equine homologue of LFA-1 (CD11a/CD18): cellular distribution and differential determinants.

  1998cites this paper
• A Binding Interface on the I Domain of Lymphocyte Function-associated Antigen-1 (LFA-1) Required for Specific Interaction with Intercellular Adhesion Molecule 1 (ICAM-1) (*)

  1995cites this paper
• Expression of CD11/CD18 and ICAM‐1 on monocytes and lymphocytes of HIV‐1‐infected individuals

  1994cites this paper
• Monoclonal antibody to the β-chain of the LFA-1 molecule can enhance the cytotoxicity of immune splenocytes by stimulating their proliferative response

  1993cites this paper
• Biological response modifiers render tumor cells susceptible to autologous effector mechanisms by influencing adhesion receptors.

  1993cites this paper
• Overview of CTL-Target Adhesion and Other Critical Events in the Cytotoxic Mechanism

  1993cites this paper
• Monoclonal antibodies to LFA-I molecule beta-chain promote a rise in the cytotoxic index of effector cells and stimulate their proliferation

  1993cites this paper
• Adhesion Molecules and Their Possible Influence on Immune Surveillance

  1992cites this paper
• Adhesion molecules on freshly recovered T leukemias promote tumor-directed lympholysis.

  1992cites this paper
• Multiple integrins share the ability to induce elevation of intracellular pH.

  1991cites this paper
• Regulation and Functional Involvement of Distinct Determinants of Leucocyte Function‐Associated Antigen 1 (LFA‐1) in T‐Cell Activation In Vitro

  1991cites this paper
• Lymphocyte Function-Associated Antigen-1 (LFA-1) Is a Signaling Molecule for Human T Lymphocytes

  1990cites this paper
• Characterization and utilization of a monoclonal antibody inhibiting porcine natural killer cell activity for isolation of natural killer and killer cells.

  1990cites this paper
• Activation of monocytic cells by monoclonal antibodies to the CD11a/18 (LFA-1) complex: mediation by Fc receptor.

  1990cites this paper
• On the mode of action of LFA-1.

  1990cites this paper
• Identification of a new cell surface glycoprotein with accessory function in murine T cell responses.

  1990cites this paper
• Soluble and surface-bound immunoglobulin triggers human monocyte activation and hydrogen peroxide release.

  1990cites this paper
• ICAM-1 (CD54): a counter-receptor for Mac-1 (CD11b/CD18)

  1990cites this paper
• History and implications of the neutrophil glycoprotein deficiencies

  1989cites this paper
• Monoclonal antibodies specific for murine CD2 reveal its presence on B as well as T cells.

  1989cites this paper
• Production and characterization of monoclonal anti-CD18 anti-idiotype antibodies.

  1989cites this paper
• Temperature requirements and kinetics of T cell signaling. Velocity of triggering correlates with functional effects of anti-CD3 mAb.

  1989cites this paper
• Expression of LFA‐1 in non‐hodgkin's lymphoma

  1989cites this paper
• The cellular immunotherapy of cancer: current and potential uses of interleukin-2.

  1989cites this paper
• Monoclonal antibodies against porcine LFA-1: species cross-reactivity and functional effects of beta-subunit-specific antibodies.

  1989cites this paper
• T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1

  1989cites this paper
• Monoclonal antibodies to CD18 and CD11A (LFA-1) distinguish Down's syndrome (trisomy 21) from normal lymphoblastoid cells.

  1989cites this paper
• LFA1 expression in HIV infection.

  1988cites this paper
• Transient decrease in IL-2-responsive lymphocytes 24 hours after initiation of continuous IL-2 infusion in cancer patients.

  1988cites this paper
• Modulation of surface CD11/CD18 glycoproteins (Mo1, LFA-1, p150,95) by human mononuclear phagocytes.

  1988cites this paper
• IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity.

  1988cites this paper
• Functional domains of the CD11a adhesion molecule in lymphokine activated killer (LAK)-mediated cytolysis.

  1988cites this paper
• The expression of CD18 is increased on Trisomy 21 (Down syndrome) lymphoblastoid cells.

  1988cites this paper
• The role of CD18 in phorbol ester-induced human monocyte-mediated cytotoxicity.

  1988cites this paper
• Murine hematopoietic cell surface antigen expression.

  1988cites this paper
• Relative contribution of the leukocyte molecules MO1, LFA‐1, and p150,95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissue‐ and stimulus‐specific

  1988cites this paper
• Studies on the Role of Lymphocyte Function‐Associated Antigen 1 (LFA‐1) in T Cell Activation

  1988cites this paper
• MEMBRANE GLYCOPROTEIN p i50,95 OF HUMAN CYTOTOXIC T CELL CLONES IS INVOLVED IN CONJUGATE FORMATION WITH TARGET CELLS1

  1987cites this paper
• Membrane glycoprotein p150,95 of human cytotoxic T cell clone is involved in conjugate formation with target cells.

  1987cites this paper
• Deficiency of leukocyte surface glycoproteins Mo1, LFA-1, and Leu M5 in a dog with recurrent bacterial infections: an animal model.

  1987cites this paper
• The Cytotoxic Lymphokines Elaborated by Effector T Cells

  1987cites this paper
• CTL adhesion and antigen recognition are discrete steps in the human CTL-target cell interaction.

  1987cites this paper
• Human complement receptor type 3.

  1987cites this paper
• Characterization of dual-reactive H-2Kb-restricted anti-vesicular stomatitus virus and alloreactive cytotoxic T cells.

  1987cites this paper
• LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes.

  1987cites this paper
• Lymphocyte function-associated antigen 1 (LFA-1) and natural killer (NK) cell activity: LFA-1 is not necessary for all killer: target cell interactions.

  1987cites this paper
• Alpha and beta subunits of the LFA‐1 membrane molecule are involved in human monocyte–endothelial cell adhesion

  1987cites this paper
• Monoclonal Antibodies That Identify Mo1 and LFA-1, Two Human Leukocyte Membrane Glycoproteins: A Review

  1986cites this paper
• Function and cell distribution of KC-1, a novel natural killer cell-associated antigen.

  1986cites this paper
• Interferon-gamma induction of LFA-1-mediated homotypic adhesion of human monocytes.

  1986cites this paper
• Cytotoxic lymphokines produced by cloned human cytotoxic T lymphocytes. II. A novel CTL-produced cytotoxin that is antigenically distinct from tumor necrosis factor and alpha-lymphotoxin.

  1986cites this paper
• Serological, Immunochemical, and Functional Analysis of the Heterogeneity of the Workshop Monoclonal Antibodies Recognizing the LFA-1 Antigen

  1986cites this paper
• Role of the LFA-1 molecule in B cell differentiation.

  1986cites this paper
• The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA.

  1986cites this paper
• Expression of the leukocyte functional molecule (LFA-1) on mouse platelets.

  1986cites this paper
• Human leukocyte function‐associated antigens on lympho‐hemopoietic precursor cells

  1986cites this paper
• Lymphocyte function-associated antigen (LFA-1) is involved in B cell activation.

  1986cites this paper
• Defective membrane expression of the LFA‐1 complex may be secondary to the absence of the β chain in a child with recurrent bacterial infection

  1986cites this paper
• A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man

  1986cites this paper
• Genetic assignment of GP90, leukocyte adhesion glycoprotein to human chromosome 21

  1986cites this paper
• Studies on transferrin receptor expression in mouse plasmacytoma cells.

  1986cites this paper
• Effects of Workshop Monoclonal Antibodies on the Cytolytic Activity of Alloreactive CD4-Positive T Cell Clones

  1986cites this paper
• Antibodies Specific for the Mac-1, LFA-1, p150,95 Glycoproteins or Their Family, or for Other Granulocyte Proteins, in the 2nd International Workshop on Human Leukocyte Differentiation Antigens

  1986cites this paper
• Abnormal cytolytic activity of lymphocyte function-associated antigen-1-deficient human cytolytic T lymphocyte clones.

  1986cites this paper
• Mapping functional epitopes of the human LFA-1 glycoprotein: monoclonal antibody inhibition of NK and CTL effectors.

  1986cites this paper
• Identification of 5 topographic domains of the mouse LFA-1 molecule: subunit assignment and functional involvement in lymphoid cell interactions.

  1986cites this paper
• Leukocyte adherence-related glycoproteins LFA-1, Mo1, and p150,95: a new group of monoclonal antibodies, a new disease, and a possible opportunity to understand the molecular basis of leukocyte adherence.

  1985cites this paper
• Identification of a Cell Surface Protein Complex Mediating Phorbol Ester‐Induced Adhesion (Binding) among Human Mononuclear Leukocytes

  1985cites this paper
• Human Cytolytic T-Lymphocyte Clones and Their Function-Associated Cell Surface Molecules

  1985cites this paper
• The Ly-15 alloantigenic system: a genetically determined polymorphism of the murine lymphocyte function-associated antigen-1 molecule.

  1985cites this paper
• Deficiency of two human leukocyte surface membrane glycoproteins (Mo1 and LFA-1).

  1985cites this paper
• Functional distinctions between the LFA-1, LFA-2, and LFA-3 membrane proteins on human CTL are revealed with trypsin-pretreated target cells.

  1985cites this paper
• Lymphocyte function-associated antigens: regulation of lymphocyte adhesions in vitro and immunity in vivo.

  1985cites this paper
• Susceptibility of cytotoxic T lymphocyte (CTL) clones to inhibition by anti-T3 and anti-T4 (but not anti-LFA-1) monoclonal antibodies varies with the "avidity" of CTL-target interaction.

  1985cites this paper
• Novel antigenic determinants of the T200 glycoprotein expressed preferentially by activated cytotoxic T lymphocytes.

  1985cites this paper
• Cell Surface Antigens Involved in Human Cytolytic T Lymphocyte-mediated Cytolysis

  1985cites this paper
• Induction of cell-cell adhesion by monovalent antibodies in a germ cell culture.

  1985cites this paper
• Human, rat or mouse hybridomas secrete high levels of monoclonal antibodies following transplantation into mice with severe combined immunodeficiency disease (SCID).

  1985cites this paper
• Human neuroblastoma cell lines are susceptible to lysis by natural killer cells but not by cytotoxic T lymphocytes.

  1985cites this paper
• Functional interactions of LFA-1, T8 and alloantigen surface structures in T-cell mediated cytotoxicity.

  1985cites this paper
• Heritable lymphocyte function-associated antigen-1 deficiency: abnormalities of cytotoxicity and proliferation associated with abnormal expression of LFA-1.

  1985cites this paper
• Deficiency of the adhesive protein complex lymphocyte function antigen 1, complement receptor type 3, glycoprotein p150,95 in a girl with recurrent bacterial infections. Effects on phagocytic cells and lymphocyte functions.

  1985influential citation
• Identification of a 150-kDa membrane component which is modulated by parathyroid hormone.

  1985cites this paper
• SB-Specific CTL Clones Exhibit Functional Heterogeneity in their Susceptibility to Blocking by Anti-T3 and Anti-T4 Antibodies

  1985cites this paper
• Blocking of CTL-mediated killing by monoclonal antibodies to LFA-1 and Lyt-2, 3. II. Evidence that trypsin pretreatment of target cells removes a non-H-2 molecule important in killing.

  1985cites this paper
• The human lymphocyte function-associated (HLFA) antigen and a related macrophage differentiation antigen (HMac-1): functional effects of subunit-specific monoclonal antibodies.

  1985cites this paper
• Human monocyte adherence to cultured vascular endothelium: monoclonal antibody-defined mechanisms.

  1985cites this paper
• Cytotoxic lymphokines produced by cloned human cytotoxic T lymphocytes. I. Cytotoxins produced by antigen-specific and natural killer-like CTL are dissimilar to classical lymphotoxins.

  1985cites this paper
• A monoclonal antibody (RH1-38) which inhibits multiple systems of cell-mediated cytotoxicity--II. Evidence that the epitope recognized is involved in a late step in the cytolytic mechanism.

  1985cites this paper
• Human lymphocyte function associated antigens

  1984cites this paper
• Deficiency of a leukocyte surface glycoprotein (LFA-1) in two patients with Mo1 deficiency. Effects of cell activation on Mo1/LFA-1 surface expression in normal and deficient leukocytes.

  1984cites this paper