lymphocyte function associated antigen 1

Summary

Summary: An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (CD18 ANTIGENS) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1.

Top Publications

  1. Salas A, Shimaoka M, Kogan A, Harwood C, von Andrian U, Springer T. Rolling adhesion through an extended conformation of integrin alphaLbeta2 and relation to alpha I and beta I-like domain interaction. Immunity. 2004;20:393-406 pubmed
  2. Perez O, Mitchell D, Jager G, Nolan G. LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells. Blood. 2004;104:1083-93 pubmed
    ..These results identify novel, specific functional consequence of LFA-1-mediated cytolytic activity in perforin-containing human NK subsets. ..
  3. Shamri R, Grabovsky V, Gauguet J, Feigelson S, Manevich E, Kolanus W, et al. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol. 2005;6:497-506 pubmed
    ..These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion. ..
  4. Chen X, Allan D, Krzewski K, Ge B, Kopcow H, Strominger J. CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells. Proc Natl Acad Sci U S A. 2006;103:10346-10351 pubmed publisher
    ..Thus, in YTS cells, a CD28 signal is used to polarize the MTOC and cytolytic granules to the NK cell immune synapse by stimulating sustained ERK2 activation. ..
  5. Ely K, Cookenham T, Roberts A, Woodland D. Memory T cell populations in the lung airways are maintained by continual recruitment. J Immunol. 2006;176:537-43 pubmed
    ..These data indicate that peripheral T cell memory is dynamic and depends on a systemic source of T cells. ..
  6. Fagerholm S, Hilden T, Nurmi S, Gahmberg C. Specific integrin alpha and beta chain phosphorylations regulate LFA-1 activation through affinity-dependent and -independent mechanisms. J Cell Biol. 2005;171:705-15 pubmed
    ..Thus, site-specific phosphorylation of the integrin cytoplasmic domains is important for the dynamic regulation of these complex receptors in cells. ..
  7. Tardif M, Tremblay M. LFA-1 is a key determinant for preferential infection of memory CD4+ T cells by human immunodeficiency virus type 1. J Virol. 2005;79:13714-24 pubmed
    ..Altogether, these data shed light on a potential mechanism by which HIV-1 preferentially targets long-lived memory CD4+ T cells. ..
  8. Jolly C, Mitar I, Sattentau Q. Adhesion molecule interactions facilitate human immunodeficiency virus type 1-induced virological synapse formation between T cells. J Virol. 2007;81:13916-21 pubmed
    ..Thus, cognate adhesion molecule interactions at the VS are important for HIV-1 spread between T cells. ..
  9. Rayat G, Gill R. Indefinite survival of neonatal porcine islet xenografts by simultaneous targeting of LFA-1 and CD154 or CD45RB. Diabetes. 2005;54:443-51 pubmed

More Information

Publications62

  1. Caputo K, Hammer D. Adhesive dynamics simulation of G-protein-mediated chemokine-activated neutrophil adhesion. Biophys J. 2009;96:2989-3004 pubmed publisher
  2. Nishida N, Xie C, Shimaoka M, Cheng Y, Walz T, Springer T. Activation of leukocyte beta2 integrins by conversion from bent to extended conformations. Immunity. 2006;25:583-94 pubmed
    ..The results establish an intimate relationship between extension of beta(2) integrins and their activation in immune responses and leukocyte trafficking. ..
  3. Giblin P, Lemieux R. LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics. Curr Pharm Des. 2006;12:2771-95 pubmed
  4. Kobayashi T, Harb G, Rayat G. Prolonged survival of microencapsulated neonatal porcine islets in mice treated with a combination of anti-CD154 and anti-LFA-1 monoclonal antibodies. Transplantation. 2005;80:821-7 pubmed
    ..These data demonstrate that short-term administration of anti-CD154 and anti-LFA-1 monoclonal antibodies can be effective in promoting long-term survival of microencapsulated NPI in immune-competent mice. ..
  5. Lin J, Miller M, Shaw A. The c-SMAC: sorting it all out (or in). J Cell Biol. 2005;170:177-82 pubmed
    ..Here, we review recently published work and propose several possible functions for the role of the c-SMAC in T cell activation. ..
  6. Tardif M, Tremblay M. Regulation of LFA-1 activity through cytoskeleton remodeling and signaling components modulates the efficiency of HIV type-1 entry in activated CD4+ T lymphocytes. J Immunol. 2005;175:926-35 pubmed
    ..Overall, these data provide new insights into the complex molecular events involved in HIV-1 binding and entry. ..
  7. Semmrich M, Smith A, Feterowski C, Beer S, Engelhardt B, Busch D, et al. Importance of integrin LFA-1 deactivation for the generation of immune responses. J Exp Med. 2005;201:1987-98 pubmed
    ..Thus, deactivation of LFA-1 and disassembly of LFA-1-mediated cell contacts seem to be vital for the generation of normal immune responses. ..
  8. Kellersch B, Kolanus W. Membrane-proximal signaling events in beta-2 integrin activation. Results Probl Cell Differ. 2006;43:245-57 pubmed
    ..This review will highlight recent developments on transmembrane and intracellular signaling proteins, which have been implicated in beta-2 integrin activation. ..
  9. Mace E, Monkley S, Critchley D, Takei F. A dual role for talin in NK cell cytotoxicity: activation of LFA-1-mediated cell adhesion and polarization of NK cells. J Immunol. 2009;182:948-56 pubmed
    ..Thus, talin1 plays a dual role in NK cell cytotoxicity, first by activation of LFA-1-mediated adhesion and then via LFA-1-induced NK cell polarization. ..
  10. Kumagai Braesch M, Ekberg H, Wang F, Osterholm C, Ehrnfelt C, Sharma A, et al. Anti-LFA-1 improves pig islet xenograft function in diabetic mice when long-term acceptance is induced by CTLA4Ig/anti-CD40L. Transplantation. 2007;83:1259-67 pubmed
    ..However, both costimulation blockade regimens led to islet graft acceptance up to 5 months after a 1-week treatment. ..
  11. Vincenti F, Mendez R, Pescovitz M, Rajagopalan P, Wilkinson A, Butt K, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant. 2007;7:1770-7 pubmed
    ..The two doses of efalizumab resulted in comparable saturation and modulation of CD11a. This phase II trial suggests that efalizumab may warrant further investigation in transplantation. ..
  12. Smith A, Stanley P, Jones K, Svensson L, McDowall A, Hogg N. The role of the integrin LFA-1 in T-lymphocyte migration. Immunol Rev. 2007;218:135-46 pubmed
  13. Atarashi K, Hirata T, Matsumoto M, Kanemitsu N, Miyasaka M. Rolling of Th1 cells via P-selectin glycoprotein ligand-1 stimulates LFA-1-mediated cell binding to ICAM-1. J Immunol. 2005;174:1424-32 pubmed
    ..These results support the idea that PSGL-1-mediated rolling interactions induce intracellular signals leading to integrin activation, facilitating Th1 cell arrest and subsequent migration into target tissues. ..
  14. Chesnutt B, Smith D, Raffler N, Smith M, White E, Ley K. Induction of LFA-1-dependent neutrophil rolling on ICAM-1 by engagement of E-selectin. Microcirculation. 2006;13:99-109 pubmed
    ..The data show that neutrophil rolling on E-selectin leads to partial activation of LFA-1, enabling LFA-1-dependent rolling on ICAM-1. This mechanism is likely to amplify and accelerate neutrophil recruitment in inflammation. ..
  15. Cambi A, Joosten B, Koopman M, de Lange F, Beeren I, Torensma R, et al. Organization of the integrin LFA-1 in nanoclusters regulates its activity. Mol Biol Cell. 2006;17:4270-81 pubmed
  16. Porter J, Falzon M, Hall A. Polarized localization of epithelial CXCL11 in chronic obstructive pulmonary disease and mechanisms of T cell egression. J Immunol. 2008;180:1866-77 pubmed
    ..This study highlights the role of the respiratory epithelium in the trafficking of T lymphocytes from the pulmonary interstitium and into the large airways, during the onset and resolution of pulmonary inflammation. ..
  17. Chen J, Yang W, Kim M, Carman C, Springer T. Regulation of outside-in signaling and affinity by the beta2 I domain of integrin alphaLbeta2. Proc Natl Acad Sci U S A. 2006;103:13062-7 pubmed
    ..Furthermore, ADMIDAS mutation abolished spreading on ligand-bearing substrates. Thus, beta(2) I domain metal ion-binding sites regulate alpha(L) I domain affinity, and the ADMIDAS is required for outside-in signaling. ..
  18. Schneider H, Valk E, da Rocha Dias S, Wei B, Rudd C. CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function. Proc Natl Acad Sci U S A. 2005;102:12861-6 pubmed
    ..Our findings identify a potent role for CTLA-4 in directing integrin adhesion and provide an alternate mechanism to account for aspects of CTLA-4 function in T cell immunity. ..
  19. Graf B, Bushnell T, Miller J. LFA-1-mediated T cell costimulation through increased localization of TCR/class II complexes to the central supramolecular activation cluster and exclusion of CD45 from the immunological synapse. J Immunol. 2007;179:1616-24 pubmed
  20. Smith A, Carrasco Y, Stanley P, Kieffer N, Batista F, Hogg N. A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. J Cell Biol. 2005;170:141-51 pubmed
    ..This adhesive structure, which differs from the previously described integrin-containing attachments displayed by many other cell types, we have termed the "focal zone." ..
  21. Kinashi T. Adhere upright: a switchblade-like extension of beta2 integrins. Immunity. 2006;25:521-2 pubmed
  22. Fett T, Zecchinon L, Baise E, Desmecht D. Cloning and characterisation of the primary structure of the sheep lymphocyte function-associated antigen-1 alpha subunit. Mol Immunol. 2005;42:1503-8 pubmed publisher
  23. Dreolini L, Takei F. Activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage. Biochem Biophys Res Commun. 2007;356:207-12 pubmed
    ..Thus, activation of LFA-1 by ionomycin is independent of calpain-mediated talin cleavage. ..
  24. Groot F, Kuijpers T, Berkhout B, de Jong E. Dendritic cell-mediated HIV-1 transmission to T cells of LAD-1 patients is impaired due to the defect in LFA-1. Retrovirology. 2006;3:75 pubmed
    ..By making use of LFA-1 defect cells from unique patients, this study provides more insight into the mechanism of HIV-1 transmission by DC. This may offer new treatment options to reduce sexual transmission of HIV-1. ..
  25. Cairo C, Mirchev R, Golan D. Cytoskeletal regulation couples LFA-1 conformational changes to receptor lateral mobility and clustering. Immunity. 2006;25:297-308 pubmed
    ..Our results suggest that current models of LFA-1 regulation are incomplete and that LFA-1 confinement by cytoskeletal attachment regulates cell adhesion both negatively and positively. ..
  26. Shimaoka M, Kim M, Cohen E, Yang W, Astrof N, Peer D, et al. AL-57, a ligand-mimetic antibody to integrin LFA-1, reveals chemokine-induced affinity up-regulation in lymphocytes. Proc Natl Acad Sci U S A. 2006;103:13991-6 pubmed
    ..Affinity up-regulation correlates with global conformational changes of LFA-1 to the extended form. Affinity increase stimulated by CXCL-12 is transient and peaks 2 to 5 min after stimulation. ..
  27. Fabbri M, Di Meglio S, Gagliani M, Consonni E, Molteni R, Bender J, et al. Dynamic partitioning into lipid rafts controls the endo-exocytic cycle of the alphaL/beta2 integrin, LFA-1, during leukocyte chemotaxis. Mol Biol Cell. 2005;16:5793-803 pubmed
  28. Tredget E, Arefanian H, Gill R, Rajotte R, Rayat G. Monotherapy with anti-LFA-1 monoclonal antibody promotes long-term survival of rat islet xenografts. Cell Transplant. 2008;17:599-608 pubmed
    ..Our study indicates that immunomodulation through mAb therapy could form a significant component of future antirejection therapies in clinical islet xenotransplantation. ..
  29. Xingyuan M, Wenyun Z, Tianwen W. Leukocyte function-associated antigen-1: structure, function and application prospects. Protein Pept Lett. 2006;13:397-400 pubmed
    ..Many different inhibitors (i.e. antibodies, peptides, small molecules) have been demonstrated to block ICAM-1/LFA-1 interaction, and some of them are promising for medical treatment or have reached clinical trials. ..
  30. Fett T, Zecchinon L, Vanden Bergh P, Desmecht D. Mannheimia haemolytica leukotoxin-induced cytolysis of caprine (Capra hircus) leukocytes is mediated by the CD18 subunit of beta2-integrins. Microb Pathog. 2008;45:337-42 pubmed publisher
    ..Taken together, these results indicate that CD18 on caprine leukocytes serves as a receptor for Lkt. ..
  31. Bergh P, Zecchinon L, Fett T, Desmecht D. The wild boar (Sus scrofa) lymphocyte function-associated antigen-1 (CD11a/CD18) receptor: cDNA sequencing, structure analysis and comparison with homologues. BMC Vet Res. 2007;3:27 pubmed
  32. Simonson W, Franco S, Huttenlocher A. Talin1 regulates TCR-mediated LFA-1 function. J Immunol. 2006;177:7707-14 pubmed
    ..Together, our findings indicate that TCR-induced up-regulation of LFA-1-dependent adhesiveness and resulting T cell-APC conjugation require talin1. ..
  33. Arefanian H, Tredget E, Rajotte R, Korbutt G, Gill R, Rayat G. Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice. Cell Transplant. 2007;16:787-98 pubmed
    ..These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice. ..
  34. Phillipson M, Heit B, Colarusso P, Liu L, Ballantyne C, Kubes P. Intraluminal crawling of neutrophils to emigration sites: a molecularly distinct process from adhesion in the recruitment cascade. J Exp Med. 2006;203:2569-75 pubmed
    ..e., LFA-1-dependent adhesion followed by Mac-1-dependent crawling, and both steps ultimately contribute to efficient emigration out of the vasculature. ..
  35. Hocdé S, Hyrien O, Waugh R. Cell adhesion molecule distribution relative to neutrophil surface topography assessed by TIRFM. Biophys J. 2009;97:379-87 pubmed publisher
    ..The results confirm differences among adhesion molecules in their surface distribution and reveal how the availability of specific adhesion molecules is altered by mechanical compression of the surface in live cells. ..
  36. Sarantos M, Raychaudhuri S, Lum A, Staunton D, Simon S. Leukocyte function-associated antigen 1-mediated adhesion stability is dynamically regulated through affinity and valency during bond formation with intercellular adhesion molecule-1. J Biol Chem. 2005;280:28290-8 pubmed
    ..These data reveal the respective importance of LFA-1 affinity and proximity in tuning bond lifetime with ICAM-1 and demonstrate a nonlinear increase in the bond lifetime of the dimer versus the monomer at higher affinity. ..
  37. Dileepan T, Thumbikat P, Walcheck B, Kannan M, Maheswaran S. Recombinant expression of bovine LFA-1 and characterization of its role as a receptor for Mannheimia haemolytica leukotoxin. Microb Pathog. 2005;38:249-57 pubmed
    ..This is the first report on recombinant expression of functionally active bovine LFA-1 by transduction into an LktA-non-susceptible human cell line. ..
  38. Song G, Yang Y, Liu J, Casasnovas J, Shimaoka M, Springer T, et al. An atomic resolution view of ICAM recognition in a complex between the binding domains of ICAM-3 and integrin alphaLbeta2. Proc Natl Acad Sci U S A. 2005;102:3366-71 pubmed
    ..Variation in composition of glycans on the periphery of the interfaces influences on-rate. ..
  39. Kim M, Carman C, Yang W, Salas A, Springer T. The primacy of affinity over clustering in regulation of adhesiveness of the integrin {alpha}L{beta}2. J Cell Biol. 2004;167:1241-53 pubmed
    ..Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands. ..
  40. Combs J, Kim S, Tan S, Ligon L, Holzbaur E, Kuhn J, et al. Recruitment of dynein to the Jurkat immunological synapse. Proc Natl Acad Sci U S A. 2006;103:14883-8 pubmed
  41. Zhang W, Shao Y, Fang D, Huang J, Jeon M, Liu Y. Negative regulation of T cell antigen receptor-mediated Crk-L-C3G signaling and cell adhesion by Cbl-b. J Biol Chem. 2003;278:23978-83 pubmed
    ..Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells. ..
  42. Vitte J, Pierres A, Benoliel A, Bongrand P. Direct quantification of the modulation of interaction between cell- or surface-bound LFA-1 and ICAM-1. J Leukoc Biol. 2004;76:594-602 pubmed
    ..It is concluded that the presented methodology provides a simple and unique way of dissecting the initial step of cell adhesion and discriminating between affinity and avidity modulation of adhesion receptors. ..
  43. Hogg N, Laschinger M, Giles K, McDowall A. T-cell integrins: more than just sticking points. J Cell Sci. 2003;116:4695-705 pubmed
    ..Another important signalling pathway acts through CasL/Crk, which might regulate the activity of the GTPases Rac and Rap1 that have important roles in T-cell migration. ..
  44. Giagulli C, Scarpini E, Ottoboni L, Narumiya S, Butcher E, Constantin G, et al. RhoA and zeta PKC control distinct modalities of LFA-1 activation by chemokines: critical role of LFA-1 affinity triggering in lymphocyte in vivo homing. Immunity. 2004;20:25-35 pubmed
    ..Thus, RhoA controls the induction of LFA-1 high-affinity state by chemokines independently of zeta PKC, and this is critical to support chemokine-regulated homing of circulating lymphocytes. ..
  45. Shimonaka M, Katagiri K, Nakayama T, Fujita N, Tsuruo T, Yoshie O, et al. Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow. J Cell Biol. 2003;161:417-27 pubmed
    ..Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation. ..
  46. Katagiri K, Shimonaka M, Kinashi T. Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. J Biol Chem. 2004;279:11875-81 pubmed
    ..Our results demonstrate that TCR activation of Rap1 depends on PLC-gamma1. This activity is likely to be mediated by CalDAG-GEFI, which is required to activate LFA-1. ..
  47. Jolly C, Kashefi K, Hollinshead M, Sattentau Q. HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med. 2004;199:283-93 pubmed
    ..We propose that receptor engagement by Env directs the rapid, actin-dependent recruitment of HIV receptors and adhesion molecules to the interface, resulting in a stable adhesive junction across which HIV infects the target cell. ..
  48. Sánchez Martín L, Sanchez Sanchez N, Gutierrez Lopez M, Rojo A, Vicente Manzanares M, Pérez Alvarez M, et al. Signaling through the leukocyte integrin LFA-1 in T cells induces a transient activation of Rac-1 that is regulated by Vav and PI3K/Akt-1. J Biol Chem. 2004;279:16194-205 pubmed
  49. Carman C, Jun C, Salas A, Springer T. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1. J Immunol. 2003;171:6135-44 pubmed
    ..This finding leaves open a possible role in leukocyte transendothelial migration, which would be consistent with the geometry and kinetics of formation of the cup-like structure. ..
  50. Shimaoka M, Salas A, Yang W, Weitz Schmidt G, Springer T. Small molecule integrin antagonists that bind to the beta2 subunit I-like domain and activate signals in one direction and block them in the other. Immunity. 2003;19:391-402 pubmed
  51. Smith A, Bracke M, Leitinger B, Porter J, Hogg N. LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment. J Cell Sci. 2003;116:3123-33 pubmed
    ..These two actomyosin-dependent processes operate coordinately to cause forward migration of a T cell. ..
  52. Giguere J, Tremblay M. Statin compounds reduce human immunodeficiency virus type 1 replication by preventing the interaction between virion-associated host intercellular adhesion molecule 1 and its natural cell surface ligand LFA-1. J Virol. 2004;78:12062-5 pubmed
    ..The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection. ..
  53. Arias R, Muñoz L, Muñoz Fernandez M. Transmission of HIV-1 infection between trophoblast placental cells and T-cells take place via an LFA-1-mediated cell to cell contact. Virology. 2003;307:266-77 pubmed
    ..This provides an explanation of the virus passing through the placental barrier during in utero HIV-1 vertical transmission. ..