Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1987 Oct 1;166(4):923–932. doi: 10.1084/jem.166.4.923

Primary structure of lymphocyte function-associated antigen 3 (LFA-3). The ligand of the T lymphocyte CD2 glycoprotein

PMCID: PMC2188720  PMID: 3309127

Abstract

We have isolated the cDNA for human lymphocyte function-associated antigen 3 (LFA-3), the ligand of the T lymphocyte CD2 molecule. The identity of the clones was established by comparison of the deduced amino acid sequence to the LFA-3 NH2-terminal and tryptic peptide sequences. The cDNA defines a mature protein of 222 amino acids that structurally resembles typical membrane-anchored proteins. An extracellular domain with six N-linked glycosylation sites is followed by a hydrophobic putative transmembrane region and a short cytoplasmic domain. The mature glycoprotein is estimated to be 44-68% carbohydrate. Southern blots of human genomic DNA indicate that only one gene codes for human LFA-3. Northern blot analysis demonstrates that the LFA-3 mRNA of 1.3 kb is widely distributed in human tissues and cell lines.

Full Text

The Full Text of this article is available as a PDF (802.0 KB).

Selected References

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

  1. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  2. Cate R. L., Chick W., Gilbert W. Comparison of the methylation patterns of the two rat insulin genes. J Biol Chem. 1983 May 25;258(10):6645–6652. [PubMed] [Google Scholar]
  3. Cate R. L., Mattaliano R. J., Hession C., Tizard R., Farber N. M., Cheung A., Ninfa E. G., Frey A. Z., Gash D. J., Chow E. P. Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986 Jun 6;45(5):685–698. doi: 10.1016/0092-8674(86)90783-x. [DOI] [PubMed] [Google Scholar]
  4. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  5. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Diehl V., Kirchner H. H., Schaadt M., Fonatsch C., Stein H., Gerdes J., Boie C. Hodgkin's disease: establishment and characterization of four in vitro cell lies. J Cancer Res Clin Oncol. 1981;101(1):111–124. doi: 10.1007/BF00405072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dustin M. L., Sanders M. E., Shaw S., Springer T. A. Purified lymphocyte function-associated antigen 3 binds to CD2 and mediates T lymphocyte adhesion. J Exp Med. 1987 Mar 1;165(3):677–692. doi: 10.1084/jem.165.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldstein M., Hoxie J., Zembryki D., Matthews D., Levinson A. I. Phenotypic and functional analysis of B cell lines from patients with multiple myeloma. Blood. 1985 Aug;66(2):444–446. [PubMed] [Google Scholar]
  9. Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
  10. Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
  11. Hunkapiller M. W., Lujan E., Ostrander F., Hood L. E. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. doi: 10.1016/s0076-6879(83)91019-4. [DOI] [PubMed] [Google Scholar]
  12. Hünig T., Tiefenthaler G., Meyer zum Büschenfelde K. H., Meuer S. C. Alternative pathway activation of T cells by binding of CD2 to its cell-surface ligand. Nature. 1987 Mar 19;326(6110):298–301. doi: 10.1038/326298a0. [DOI] [PubMed] [Google Scholar]
  13. Krensky A. M., Robbins E., Springer T. A., Burakoff S. J. LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation. J Immunol. 1984 May;132(5):2180–2182. [PubMed] [Google Scholar]
  14. 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]
  15. Lipman D. J., Pearson W. R. Rapid and sensitive protein similarity searches. Science. 1985 Mar 22;227(4693):1435–1441. doi: 10.1126/science.2983426. [DOI] [PubMed] [Google Scholar]
  16. Low M. G. Biochemistry of the glycosyl-phosphatidylinositol membrane protein anchors. Biochem J. 1987 May 15;244(1):1–13. doi: 10.1042/bj2440001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  18. Okayama H., Berg P. High-efficiency cloning of full-length cDNA. Mol Cell Biol. 1982 Feb;2(2):161–170. doi: 10.1128/mcb.2.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Parham P., Alpert B. N., Orr H. T., Strominger J. L. Carbohydrate moiety of HLA antigens. Antigenic properties and amino acid sequences around the site of glycosylation. J Biol Chem. 1977 Nov 10;252(21):7555–7567. [PubMed] [Google Scholar]
  20. Pederson D. S., Thoma F., Simpson R. T. Core particle, fiber, and transcriptionally active chromatin structure. Annu Rev Cell Biol. 1986;2:117–147. doi: 10.1146/annurev.cb.02.110186.001001. [DOI] [PubMed] [Google Scholar]
  21. Pepinsky R. B., Sinclair L. K., Browning J. L., Mattaliano R. J., Smart J. E., Chow E. P., Falbel T., Ribolini A., Garwin J. L., Wallner B. P. Purification and partial sequence analysis of a 37-kDa protein that inhibits phospholipase A2 activity from rat peritoneal exudates. J Biol Chem. 1986 Mar 25;261(9):4239–4246. [PubMed] [Google Scholar]
  22. Plunkett M. L., Sanders M. E., Selvaraj P., Dustin M. L., Springer T. A. Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function-associated antigen 3 (LFA-3). J Exp Med. 1987 Mar 1;165(3):664–676. doi: 10.1084/jem.165.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ruoslahti E., Pierschbacher M. D. Arg-Gly-Asp: a versatile cell recognition signal. Cell. 1986 Feb 28;44(4):517–518. doi: 10.1016/0092-8674(86)90259-x. [DOI] [PubMed] [Google Scholar]
  24. Sayre P. H., Chang H. C., Hussey R. E., Brown N. R., Richardson N. E., Spagnoli G., Clayton L. K., Reinherz E. L. Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(9):2941–2945. doi: 10.1073/pnas.84.9.2941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scala G., Kuang Y. D., Hall R. E., Muchmore A. V., Oppenheim J. J. Accessory cell function of human B cells. I. Production of both interleukin 1-like activity and an interleukin 1 inhibitory factor by an EBV-transformed human B cell line. J Exp Med. 1984 Jun 1;159(6):1637–1652. doi: 10.1084/jem.159.6.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Seed B., Aruffo A. Molecular cloning of the CD2 antigen, the T-cell erythrocyte receptor, by a rapid immunoselection procedure. Proc Natl Acad Sci U S A. 1987 May;84(10):3365–3369. doi: 10.1073/pnas.84.10.3365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Selvaraj P., Dustin M. L., Silber R., Low M. G., Springer T. A. Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor. J Exp Med. 1987 Oct 1;166(4):1011–1025. doi: 10.1084/jem.166.4.1011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Selvaraj P., Plunkett M. L., Dustin M., Sanders M. E., Shaw S., Springer T. A. The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. 1987 Mar 26-Apr 1Nature. 326(6111):400–403. doi: 10.1038/326400a0. [DOI] [PubMed] [Google Scholar]
  29. Sewell W. A., Brown M. H., Dunne J., Owen M. J., Crumpton M. J. Molecular cloning of the human T-lymphocyte surface CD2 (T11) antigen. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8718–8722. doi: 10.1073/pnas.83.22.8718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shaw S., Luce G. E., Quinones R., Gress R. E., Springer T. A., Sanders M. E. Two antigen-independent adhesion pathways used by human cytotoxic T-cell clones. Nature. 1986 Sep 18;323(6085):262–264. doi: 10.1038/323262a0. [DOI] [PubMed] [Google Scholar]
  31. Vollger L. W., Tuck D. T., Springer T. A., Haynes B. F., Singer K. H. Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. J Immunol. 1987 Jan 15;138(2):358–363. [PubMed] [Google Scholar]
  32. Williams A. F., Barclay A. N., Clark S. J., Paterson D. J., Willis A. C. Similarities in sequences and cellular expression between rat CD2 and CD4 antigens. J Exp Med. 1987 Feb 1;165(2):368–380. doi: 10.1084/jem.165.2.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wong W. W., Klickstein L. B., Smith J. A., Weis J. H., Fearon D. T. Identification of a partial cDNA clone for the human receptor for complement fragments C3b/C4b. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7711–7715. doi: 10.1073/pnas.82.22.7711. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES