CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics

The structurally related T cell surface molecules CD28 and CTLA-4 interact with cell surface ligands CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells (APC) and modulate T cell antigen recognition. Preliminary reports have suggested that CD80 binds CTLA-4 and CD28 with affinities (K d values ∼12 and ∼200 nM, respectively) that are high when compared with other molecular interactions that contribute to T cell–APC recognition. In the present study, we use surface plasmon resonance to measure the affinity and kinetics of CD80 binding to CD28 and CTLA-4. At 37°C, soluble recombinant CD80 bound to CTLA-4 and CD28 with K d values of 0.42 and 4 μM, respectively. Kinetic analysis indicated that these low affinities were the result of very fast dissociation rate constants (koff); sCD80 dissociated from CD28 and CTLA-4 with koff values of ⩾1.6 and ⩾0.43 s−1, respectively. Such rapid binding kinetics have also been reported for the T cell adhesion molecule CD2 and may be necessary to accommodate dynamic T cell–APC contacts and to facilitate scanning of APC for antigen.

[1]  M. Allen,et al.  Human Influence on the Atmospheric Vertical Temperature Structure: Detection and Observations , 1996, Science.

[2]  P. Linsley,et al.  Covalent Dimerization of CD28/CTLA-4 and Oligomerization of CD80/CD86 Regulate T Cell Costimulatory Interactions* , 1996, The Journal of Biological Chemistry.

[3]  Antonio Lanzavecchia,et al.  T Cell Activation Determined by T Cell Receptor Number and Tunable Thresholds , 1996, Science.

[4]  S. Jameson,et al.  T-cell-receptor affinity and thymocyte positive selection , 1996, Nature.

[5]  J. Bluestone,et al.  CTLA-4 ligation blocks CD28-dependent T cell activation [published erratum appears in J Exp Med 1996 Jul 1;184(1):301] , 1996, The Journal of experimental medicine.

[6]  T. Mak,et al.  Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association with CTLA-4 , 1996, Science.

[7]  J. Bluestone,et al.  CD28/B7 system of T cell costimulation. , 1996, Annual review of immunology.

[8]  A. Barclay,et al.  Analysis of cell-adhesion molecule interactions using surface plasmon resonance. , 1996, Current opinion in immunology.

[9]  D. Margulies,et al.  Studying interactions involving the T-cell antigen receptor by surface plasmon resonance. , 1996, Current opinion in immunology.

[10]  A. Lanzavecchia,et al.  Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy , 1996, The Journal of experimental medicine.

[11]  S. Davis,et al.  The structure and ligand interactions of CD2: implications for T-cell function. , 1996, Immunology today.

[12]  P. Schuck,et al.  Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor. I. A computer simulation of the influence of mass transport. , 1996, Biophysical journal.

[13]  L. Nieba,et al.  Competition BIAcore for measuring true affinities: large differences from values determined from binding kinetics. , 1996, Analytical biochemistry.

[14]  Michael Loran Dustin,et al.  Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area , 1996, The Journal of cell biology.

[15]  W. A. Rees,et al.  Biophysical studies of T-cell receptors and their ligands. , 1996, Current opinion in immunology.

[16]  R. Karr,et al.  Differential effects of CTLA-4 substitutions on the binding of human CD80 (B7-1) and CD86 (B7-2). , 1996, Journal of immunology.

[17]  D. Olive,et al.  Comparison of CD28‐B7.1 and B7.2 functional interaction in resting human T cells: Phosphatidylinositol 3‐kinase association to CD28 and cytokine production , 1996, European journal of immunology.

[18]  R. J. Cohen,et al.  The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  A. Barclay,et al.  A sensitive assay for detecting low‐affinity interactions at the cell surface reveals no additional ligands for the adhesion pair rat CD2 and CD48 , 1995, European journal of immunology.

[20]  H. Griesser,et al.  Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4 , 1995, Science.

[21]  P. A. van der Merwe,et al.  The Amino-terminal Immunoglobulin-like Domain of Sialoadhesin Contains the Sialic Acid Binding Site , 1995, The Journal of Biological Chemistry.

[22]  J. Bluestone,et al.  Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. , 1995, Immunity.

[23]  J. Allison,et al.  CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation , 1995, The Journal of experimental medicine.

[24]  R. Karr,et al.  Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. , 1995, Journal of immunology.

[25]  P. Linsley,et al.  Distinct roles for CD28 and cytotoxic T lymphocyte-associated molecule- 4 receptors during T cell activation? , 1995, The Journal of experimental medicine.

[26]  P. Linsley,et al.  Binding Stoichiometry of the Cytotoxic T Lymphocyte-associated Molecule-4 (CTLA-4) , 1995, The Journal of Biological Chemistry.

[27]  A. Lanzavecchia,et al.  Serial triggering of many T-cell receptors by a few peptide–MHC complexes , 1995, Nature.

[28]  R. Fisher,et al.  T cell receptor-MHC class I peptide interactions: affinity, kinetics, and specificity. , 1995, Science.

[29]  A. Lanzavecchia,et al.  Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton , 1995, The Journal of experimental medicine.

[30]  P. Romero,et al.  CD8 modulation of T-cell antigen receptor–ligand interactions on living cytotoxic T lymphocytes , 1995, Nature.

[31]  H. Eisen,et al.  Variations in the number of peptide-MHC class I complexes required to activate cytotoxic T cell responses. , 1995, Journal of immunology.

[32]  M. Davis,et al.  Kinetics of T-cell receptor binding to peptide/I-Ek complexes: correlation of the dissociation rate with T-cell responsiveness. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  P. Linsley,et al.  Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. , 1994, Immunity.

[34]  M. Filbin,et al.  Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily , 1994, Current Biology.

[35]  A. Barclay,et al.  Transient intercellular adhesion: the importance of weak protein-protein interactions. , 1994, Trends in biochemical sciences.

[36]  D. Mason,et al.  Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. , 1994, Biochemistry.

[37]  J. Bluestone,et al.  The B7 and CD28 receptor families. , 1994, Immunology today.

[38]  R. J. Cohen,et al.  Kinetics and affinity of reactions between an antigen-specific T cell receptor and peptide-MHC complexes. , 1994, Immunity.

[39]  Jeffrey A. Ledbetter,et al.  How B and T cells talk to each other , 1994, Nature.

[40]  D. O'Shannessy,et al.  Determination of kinetic rate and equilibrium binding constants for macromolecular interactions: a critique of the surface plasmon resonance literature. , 1994, Current opinion in biotechnology.

[41]  A. Barclay,et al.  Affinity and kinetic analysis of the interaction of the cell adhesion molecules rat CD2 and CD48. , 1993, The EMBO journal.

[42]  G. Freeman,et al.  Uncovering of functional alternative CTLA-4 counter-receptor in B7-deficient mice. , 1993, Science.

[43]  J. Gribben,et al.  Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. , 1993, Science.

[44]  P. Linsley,et al.  Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. , 1993, Science.

[45]  L. Lanier,et al.  B70 antigen is a second ligand for CTLA-4 and CD28 , 1993, Nature.

[46]  J. Cyster,et al.  Structural analysis of the CD2 T lymphocyte antigen by site-directed mutagenesis to introduce a disulphide bond into domain 1. , 1993, Protein engineering.

[47]  K. Karjalainen,et al.  Mouse CD4 binds MHC class II with extremely low affinity. , 1993, International immunology.

[48]  D. Olive,et al.  CD28 mAbs with distinct binding properties differ in their ability to induce T cell activation: analysis of early and late activation events. , 1993, International immunology.

[49]  P. Linsley,et al.  Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes , 1992, The Journal of experimental medicine.

[50]  J. Guardiola,et al.  Identification of a CD4 binding site on the β2 domain of HLA-DR molecules , 1992, Nature.

[51]  M. Davis,et al.  Low affinity interaction of peptide-MHC complexes with T cell receptors. , 1991, Science.

[52]  R. Karlsson,et al.  Kinetic analysis of monoclonal antibody-antigen interactions with a new biosensor based analytical system. , 1991, Journal of immunological methods.

[53]  R. Karlsson,et al.  Real-time biospecific interaction analysis using surface plasmon resonance and a sensor chip technology. , 1991, BioTechniques.

[54]  P. Linsley,et al.  CTLA-4 is a second receptor for the B cell activation antigen B7 , 1991, The Journal of experimental medicine.

[55]  M. Luscher,et al.  Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis , 1991, Nature.

[56]  C. Bebbington,et al.  Expression of antibody genes in nonlymphoid mammalian cells , 1991 .

[57]  P. Linsley,et al.  Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation , 1991, The Journal of experimental medicine.

[58]  H. Grey,et al.  The minimal number of class II MHC-antigen complexes needed for T cell activation. , 1990, Science.

[59]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[60]  P. Linsley,et al.  T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[61]  A. Barclay,et al.  High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. , 1990, The Journal of biological chemistry.

[62]  J. Banchereau,et al.  mAb 104, a new monoclonal antibody, recognizes the B7 antigen that is expressed on activated B cells and HTLV-1-transformed T cells. , 1990, Immunology.

[63]  G. Freeman,et al.  B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. , 1989, Journal of immunology.

[64]  H. Marquardt,et al.  Molecular cloning, sequence analysis, and functional expression of a novel growth regulator, oncostatin M , 1989, Molecular and cellular biology.

[65]  B. Seed,et al.  Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[66]  F. Denizot,et al.  A new member of the immunoglobulin superfamily—CTLA-4 , 1987, Nature.

[67]  W. Jefferies,et al.  Peptide and nucleotide sequences of rat CD4 (W3/25) antigen: evidence for derivation from a structure with four immunoglobulin-related domains. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Yokoyama,et al.  [A new monoclonal antibody (KOLT-2) specific to the cell surface antigen on activated human T lymphocytes]. , 1984, Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society.

[69]  T. Yokochi,et al.  B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt's lymphomas. , 1982, Journal of immunology.

[70]  G. I. Bell.  Models for the specific adhesion of cells to cells. , 1978, Science.

[71]  M. Bevan,et al.  T cell receptor antagonists and partial agonists. , 1995, Immunity.

[72]  Wim Timens,et al.  Leucocyte typing V. White cell differentiation antigens , 1995 .

[73]  A. Barclay,et al.  Expression of immunoglobulin and scavenger receptor superfamily domains as chimeric proteins with domains 3 and 4 of CD4 for ligand analysis. , 1994, Protein engineering.

[74]  P. Linsley,et al.  The role of the CD28 receptor during T cell responses to antigen. , 1993, Annual review of immunology.

[75]  D. Hartley.  Cellular interactions in development : a practical approach , 1993 .