Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Jun;79(6):1607–1614. doi: 10.1172/JCI112996

Polymorphism of lymphocyte function-associated antigen-1 demonstrated by a lupus patient's alloantiserum.

K D Pischel, S D Marlin, T A Springer, V L Woods Jr, H G Bluestein
PMCID: PMC424480  PMID: 2438304

Abstract

We have found a human serum, E27, obtained from a multiply transfused patient with systemic lupus erythematosus, which immunoprecipitates the lymphocyte function associated antigen-1 (LFA-1). The immunoprecipitated molecules were identified as the LFA-1 alpha and beta chains by their comigration on SDS-PAGE, two-dimensional SDS-PAGE, and by sequential clearance experiments. Serum E27 did not immunoprecipitate LFA-1 from autologous cells, though LFA-1 molecules were present. In contrast, serum E27 immunoprecipitated LFA-1 from most but not all normal donor lymphocytes. Thus, serum E27 defines two serological phenotypes of LFA-1. 95% of normal individuals tested exhibited the LFA-1 phenotype precipitated by serum E27. Serum E27 appears to be directed at determinants of the LFA-1 alpha-chain and not the beta-chain since it immunoprecipitated LFA-1 molecules but not the Mac-1 molecules. Additional evidence for the alpha chain specificity was provided by immunoprecipitation of mouse-human heterohybridoma cells. LFA-1 was immunoprecipitated by serum E27 from mouse-human heterohybridoma cells expressing the human alpha-chain, not from a hybrid cell line expressing the human beta-chain. Together these findings demonstrate an antigenic polymorphism of the human LFA-1 alpha-chain molecule.

Full text

PDF
1607

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abramson J. S., Mills E. L., Sawyer M. K., Regelmann W. R., Nelson J. D., Quie P. G. Recurrent infections and delayed separation of the umbilical cord in an infant with abnormal phagocytic cell locomotion and oxidative response during particle phagocytosis. J Pediatr. 1981 Dec;99(6):887–894. doi: 10.1016/s0022-3476(81)80011-x. [DOI] [PubMed] [Google Scholar]
  2. Anderson D. C., Schmalstieg F. C., Arnaout M. A., Kohl S., Tosi M. F., Dana N., Buffone G. J., Hughes B. J., Brinkley B. R., Dickey W. D. Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence. J Clin Invest. 1984 Aug;74(2):536–551. doi: 10.1172/JCI111451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Anderson D. C., Schmalstieg F. C., Shearer W., Becker-Freeman K., Kohl S., Smith C. W., Tosi M. F., Springer T. Leukocyte LFA-1, OKM1, p150,95 deficiency syndrome: functional and biosynthetic studies of three kindreds. Fed Proc. 1985 Jul;44(10):2671–2677. [PubMed] [Google Scholar]
  4. Arnaout M. A., Dana N., Pitt J., Todd R. F., 3rd Deficiency of two human leukocyte surface membrane glycoproteins (Mo1 and LFA-1). Fed Proc. 1985 Jul;44(10):2664–2670. [PubMed] [Google Scholar]
  5. Arnaout M. A., Pitt J., Cohen H. J., Melamed J., Rosen F. S., Colten H. R. Deficiency of a granulocyte-membrane glycoprotein (gp150) in a boy with recurrent bacterial infections. N Engl J Med. 1982 Mar 25;306(12):693–699. doi: 10.1056/NEJM198203253061201. [DOI] [PubMed] [Google Scholar]
  6. Baur S., Vitetta E. S., Sherr C. J., Schenkein I., Uhr J. W. Isolation of heavy and light chains of immunoglobulin from the surfaces of lymphoid cells. J Immunol. 1971 Apr;106(4):1133–1135. [PubMed] [Google Scholar]
  7. Beatty P. G., Ledbetter J. A., Martin P. J., Price T. H., Hansen J. A. Definition of a common leukocyte cell-surface antigen (Lp95-150) associated with diverse cell-mediated immune functions. J Immunol. 1983 Dec;131(6):2913–2918. [PubMed] [Google Scholar]
  8. Beatty P. G., Ochs H. D., Harlan J. M., Price T. H., Rosen H., Taylor R. F., Hansen J. A., Klebanoff S. J. Absence of monoclonal-antibody-defined protein complex in boy with abnormal leucocyte function. Lancet. 1984 Mar 10;1(8376):535–537. doi: 10.1016/s0140-6736(84)90933-4. [DOI] [PubMed] [Google Scholar]
  9. Bongrand P., Pierres M., Golstein P. T cell-mediated cytolysis: on the strength of effector-target cell interaction. Eur J Immunol. 1983 May;13(5):424–429. doi: 10.1002/eji.1830130514. [DOI] [PubMed] [Google Scholar]
  10. Bowen T. J., Ochs H. D., Altman L. C., Price T. H., Van Epps D. E., Brautigan D. L., Rosin R. E., Perkins W. D., Babior B. M., Klebanoff S. J. Severe recurrent bacterial infections associated with defective adherence and chemotaxis in two patients with neutrophils deficient in a cell-associated glycoprotein. J Pediatr. 1982 Dec;101(6):932–940. doi: 10.1016/s0022-3476(82)80013-9. [DOI] [PubMed] [Google Scholar]
  11. Crowley C. A., Curnutte J. T., Rosin R. E., André-Schwartz J., Gallin J. I., Klempner M., Snyderman R., Southwick F. S., Stossel T. P., Babior B. M. An inherited abnormality of neutrophil adhesion. Its genetic transmission and its association with a missing protein. N Engl J Med. 1980 May 22;302(21):1163–1168. doi: 10.1056/NEJM198005223022102. [DOI] [PubMed] [Google Scholar]
  12. Dana N., Todd R. F., 3rd, Pitt J., Springer T. A., Arnaout M. A. Deficiency of a surface membrane glycoprotein (Mo1) in man. J Clin Invest. 1984 Jan;73(1):153–159. doi: 10.1172/JCI111186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Lymphocyte function-associated antigen 1 (LFA-1): a surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4535–4539. doi: 10.1073/pnas.78.7.4535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Davignon D., Martz E., Reynolds T., Kürzinger K., Springer T. A. Monoclonal antibody to a novel lymphocyte function-associated antigen (LFA-1): mechanism of blockade of T lymphocyte-mediated killing and effects on other T and B lymphocyte functions. J Immunol. 1981 Aug;127(2):590–595. [PubMed] [Google Scholar]
  15. Hildreth J. E., Gotch F. M., Hildreth P. D., McMichael A. J. A human lymphocyte-associated antigen involved in cell-mediated lympholysis. Eur J Immunol. 1983 Mar;13(3):202–208. doi: 10.1002/eji.1830130305. [DOI] [PubMed] [Google Scholar]
  16. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  17. Kohl S., Springer T. A., Schmalstieg F. C., Loo L. S., Anderson D. C. Defective natural killer cytotoxicity and polymorphonuclear leukocyte antibody-dependent cellular cytotoxicity in patients with LFA-1/OKM-1 deficiency. J Immunol. 1984 Dec;133(6):2972–2978. [PubMed] [Google Scholar]
  18. Krensky A. M., Sanchez-Madrid F., Robbins E., Nagy J. A., Springer T. A., Burakoff S. J. The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions. J Immunol. 1983 Aug;131(2):611–616. [PubMed] [Google Scholar]
  19. Kürzinger K., Reynolds T., Germain R. N., Davignon D., Martz E., Springer T. A. A novel lymphocyte function-associated antigen (LFA-1): cellular distribution, quantitative expression, and structure. J Immunol. 1981 Aug;127(2):596–602. [PubMed] [Google Scholar]
  20. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  21. Marlin S. D., Morton C. C., Anderson D. C., Springer T. A. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. doi: 10.1084/jem.164.3.855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Miedema F., Tetteroo P. A., Hesselink W. G., Werner G., Spits H., Melief C. J. Both Fc receptors and lymphocyte-function-associated antigen 1 on human T gamma lymphocytes are required for antibody-dependent cellular cytotoxicity (killer cell activity). Eur J Immunol. 1984 Jun;14(6):518–523. doi: 10.1002/eji.1830140607. [DOI] [PubMed] [Google Scholar]
  23. Mogensen C. E. The glomerular permeability determined by dextran clearance using Sephadex gel filtration. Scand J Clin Lab Invest. 1968;21(1):77–82. doi: 10.3109/00365516809076979. [DOI] [PubMed] [Google Scholar]
  24. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  25. Pischel K. D., Bluestein H. G., Woods V. L., Jr Very late activation antigens (VLA) are human leukocyte-neuronal crossreactive cell surface antigens. J Exp Med. 1986 Aug 1;164(2):393–406. doi: 10.1084/jem.164.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ross G. D., Thompson R. A., Walport M. J., Springer T. A., Watson J. V., Ward R. H., Lida J., Newman S. L., Harrison R. A., Lachmann P. J. Characterization of patients with an increased susceptibility to bacterial infections and a genetic deficiency of leukocyte membrane complement receptor type 3 and the related membrane antigen LFA-1. Blood. 1985 Oct;66(4):882–890. [PubMed] [Google Scholar]
  27. Russ G. R., Haddad A. P., Tait B. D., d'Apice A. J. Polymorphism of the complement receptor for C3bi. J Clin Invest. 1985 Nov;76(5):1965–1970. doi: 10.1172/JCI112195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanchez-Madrid F., Davignon D., Martz E., Springer T. A. Antigens involved in mouse cytolytic T-lymphocyte (CTL)-mediated killing: functional screening and topographic relationship. Cell Immunol. 1982 Oct;73(1):1–11. doi: 10.1016/0008-8749(82)90431-2. [DOI] [PubMed] [Google Scholar]
  29. Sanchez-Madrid F., Krensky A. M., Ware C. F., Robbins E., Strominger J. L., Burakoff S. J., Springer T. A. Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7489–7493. doi: 10.1073/pnas.79.23.7489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sanchez-Madrid F., Nagy J. A., Robbins E., Simon P., Springer T. A. A human leukocyte differentiation antigen family with distinct alpha-subunits and a common beta-subunit: the lymphocyte function-associated antigen (LFA-1), the C3bi complement receptor (OKM1/Mac-1), and the p150,95 molecule. J Exp Med. 1983 Dec 1;158(6):1785–1803. doi: 10.1084/jem.158.6.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sanchez-Madrid F., Simon P., Thompson S., Springer T. A. Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1. J Exp Med. 1983 Aug 1;158(2):586–602. doi: 10.1084/jem.158.2.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sarmiento M., Dialynas D. P., Lancki D. W., Wall K. A., Lorber M. I., Loken M. R., Fitch F. W. Cloned T lymphocytes and monoclonal antibodies as probes for cell surface molecules active in T cell-mediated cytolysis. Immunol Rev. 1982;68:135–169. doi: 10.1111/j.1600-065x.1982.tb01063.x. [DOI] [PubMed] [Google Scholar]
  33. Spits H., Keizer G., Borst J., Terhorst C., Hekman A., de Vries J. E. Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines. Hybridoma. 1983;2(4):423–437. doi: 10.1089/hyb.1983.2.423. [DOI] [PubMed] [Google Scholar]
  34. Springer T. A., Thompson W. S., Miller L. J., Schmalstieg F. C., Anderson D. C. Inherited deficiency of the Mac-1, LFA-1, p150,95 glycoprotein family and its molecular basis. J Exp Med. 1984 Dec 1;160(6):1901–1918. doi: 10.1084/jem.160.6.1901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Thompson R. A., Candy D. C., McNeish A. S. Familial defect of polymorph neutrophil phagocytosis associated with absence of a surface glycoprotein antigen (OKMI). Clin Exp Immunol. 1984 Oct;58(1):229–236. [PMC free article] [PubMed] [Google Scholar]
  36. Todd R. F., 3rd, Arnaout M. A., Rosin R. E., Crowley C. A., Peters W. A., Babior B. M. Subcellular localization of the large subunit of Mo1 (Mo1 alpha; formerly gp 110), a surface glycoprotein associated with neutrophil adhesion. J Clin Invest. 1984 Oct;74(4):1280–1290. doi: 10.1172/JCI111538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Trowbridge I. S., Omary M. B. Molecular complexity of leukocyte surface glycoproteins related to the macrophage differentiation antigen Mac-1. J Exp Med. 1981 Nov 1;154(5):1517–1524. doi: 10.1084/jem.154.5.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES