Abstract
Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune diseases and the prevention of infections and of graft versus host reactions in recipients of allogeneic bone marrow transplants. The immunomodulatory effects of IVIg are largely dependent on their ability to interact with membrane molecules of lymphocytes. We report here that IVIg recognizes the B07.75-84 peptide, corresponding to a conserved region of the alpha I helix of the first domain of HLA-B7 01, which represents a nonpolymorphic determinant of HLA class I molecules. Intact IVIg and its F(ab')2 fragments bound to the peptide as well as to purified soluble HLA and to HLA on a human T cell line. Binding of IVIg to HLA was assessed by ELISA, immunofluorescence, and real-time analysis of the interaction using the BIAlite system. The binding of antipeptide antibodies to HLA was inhibited by free peptide. Antipeptide antibodies isolated from IVIg by affinity chromatography inhibited CD8 cell-mediated cytotoxicity of an influenza virus-specific human T cell line. The presence in IVIg of antibodies to critical regions of HLA class 1 molecules suggests a possible role for IVIg in modulation of class-I-restricted cellular interactions in the immune response.
Full Text
The Full Text of this article is available as a PDF (167.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Amran D., Renz H., Lack G., Bradley K., Gelfand E. W. Suppression of cytokine-dependent human T-cell proliferation by intravenous immunoglobulin. Clin Immunol Immunopathol. 1994 Nov;73(2):180–186. doi: 10.1006/clin.1994.1186. [DOI] [PubMed] [Google Scholar]
- Avrameas S., Guilbert B., Dighiero G. Natural antibodies against tubulin, actin myoglobin, thyroglobulin, fetuin, albumin and transferrin are present in normal human sera, and monoclonal immunoglobulins from multiple myeloma and Waldenström's macroglobulinemia may express similar antibody specificities. Ann Immunol (Paris) 1981 Mar-Apr;132C(2):231–236. doi: 10.1016/0769-2625(81)90031-3. [DOI] [PubMed] [Google Scholar]
- Bass E. B., Powe N. R., Goodman S. N., Graziano S. L., Griffiths R. I., Kickler T. S., Wingard J. R. Efficacy of immune globulin in preventing complications of bone marrow transplantation: a meta-analysis. Bone Marrow Transplant. 1993 Sep;12(3):273–282. [PubMed] [Google Scholar]
- Berneman A., Guilbert B., Eschrich S., Avrameas S. IgG auto- and polyreactivities of normal human sera. Mol Immunol. 1993 Nov;30(16):1499–1510. doi: 10.1016/0161-5890(93)90458-n. [DOI] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
- Blasczyk R., Westhoff U., Grosse-Wilde H. Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations. Lancet. 1993 Mar 27;341(8848):789–790. doi: 10.1016/0140-6736(93)90563-v. [DOI] [PubMed] [Google Scholar]
- Bourgault I., Gomez A., Gomard E., Picard F., Levy J. P., Gomrad E. A virus-specific CD4+ cell-mediated cytolytic activity revealed by CD8+ cell elimination regularly develops in uncloned human antiviral cell lines. J Immunol. 1989 Jan 1;142(1):252–256. [PubMed] [Google Scholar]
- Buelow R., Burlingham W. J., Clayberger C. Immunomodulation by soluble HLA class I. Transplantation. 1995 Mar 15;59(5):649–654. doi: 10.1097/00007890-199503150-00001. [DOI] [PubMed] [Google Scholar]
- Clayberger C., Lyu S. C., Pouletty P., Krensky A. M. Peptides corresponding to T-cell receptor-HLA contact regions inhibit class I-restricted immune responses. Transplant Proc. 1993 Feb;25(1 Pt 1):477–478. [PubMed] [Google Scholar]
- Delfraissy J. F., Tchernia G., Laurian Y., Wallon C., Galanaud P., Dormont J. Suppressor cell function after intravenous gammaglobulin treatment in adult chronic idiopathic thrombocytopenic purpura. Br J Haematol. 1985 Jun;60(2):315–322. doi: 10.1111/j.1365-2141.1985.tb07417.x. [DOI] [PubMed] [Google Scholar]
- Dietrich G., Kazatchkine M. D. Normal immunoglobulin G (IgG) for therapeutic use (intravenous Ig) contain antiidiotypic specificities against an immunodominant, disease-associated, cross-reactive idiotype of human anti-thyroglobulin autoantibodies. J Clin Invest. 1990 Mar;85(3):620–625. doi: 10.1172/JCI114483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dwyer J. M. Manipulating the immune system with immune globulin. N Engl J Med. 1992 Jan 9;326(2):107–116. doi: 10.1056/NEJM199201093260206. [DOI] [PubMed] [Google Scholar]
- Gaur A., Fathman C. G. Immunotherapeutic strategies directed at the trimolecular complex. Adv Immunol. 1994;56:219–265. doi: 10.1016/s0065-2776(08)60453-8. [DOI] [PubMed] [Google Scholar]
- Glotz D., Haymann J. P., Niaudet P., Lang P., Druet P., Bariety J. Successful kidney transplantation of immunized patients after desensitization with normal human polyclonal immunoglobulins. Transplant Proc. 1995 Feb;27(1):1038–1039. [PubMed] [Google Scholar]
- Glotz D., Haymann J. P., Sansonetti N., Francois A., Menoyo-Calonge V., Bariety J., Druet P. Suppression of HLA-specific alloantibodies by high-dose intravenous immunoglobulins (IVIg). A potential tool for transplantation of immunized patients. Transplantation. 1993 Aug;56(2):335–337. doi: 10.1097/00007890-199308000-00015. [DOI] [PubMed] [Google Scholar]
- Glowacki L. S., Smaill F. M. Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients--a meta-analysis. Clin Transplant. 1994 Feb;8(1):10–18. [PubMed] [Google Scholar]
- Guilbert B., Dighiero G., Avrameas S. Naturally occurring antibodies against nine common antigens in human sera. I. Detection, isolation and characterization. J Immunol. 1982 Jun;128(6):2779–2787. [PubMed] [Google Scholar]
- Hurez V., Kaveri S. V., Kazatchkine M. D. Expression and control of the natural autoreactive IgG repertoire in normal human serum. Eur J Immunol. 1993 Apr;23(4):783–789. doi: 10.1002/eji.1830230402. [DOI] [PubMed] [Google Scholar]
- Hurez V., Kaveri S. V., Mouhoub A., Dietrich G., Mani J. C., Klatzmann D., Kazatchkine M. D. Anti-CD4 activity of normal human immunoglobulin G for therapeutic use. (Intravenous immunoglobulin, IVIg). Ther Immunol. 1994 Oct;1(5):269–277. [PubMed] [Google Scholar]
- Kazatchkine M. D., Dietrich G., Hurez V., Ronda N., Bellon B., Rossi F., Kaveri S. V. V region-mediated selection of autoreactive repertoires by intravenous immunoglobulin (i.v.Ig). Immunol Rev. 1994 Jun;139:79–107. doi: 10.1111/j.1600-065x.1994.tb00858.x. [DOI] [PubMed] [Google Scholar]
- Lam L., Whitsett C. F., McNicholl J. M., Hodge T. W., Hooper J. Immunologically active proteins in intravenous immunoglobulin. Lancet. 1993 Sep 11;342(8872):678–678. doi: 10.1016/0140-6736(93)91784-j. [DOI] [PubMed] [Google Scholar]
- Marchalonis J. J., Kaymaz H., Dedeoglu F., Schluter S. F., Yocum D. E., Edmundson A. B. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3325–3329. doi: 10.1073/pnas.89.8.3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nisco S., Vriens P., Hoyt G., Lyu S. C., Farfan F., Pouletty P., Krensky A. M., Clayberger C. Induction of allograft tolerance in rats by an HLA class-I-derived peptide and cyclosporine A. J Immunol. 1994 Apr 15;152(8):3786–3792. [PubMed] [Google Scholar]
- Rossi F., Kazatchkine M. D. Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig. J Immunol. 1989 Dec 15;143(12):4104–4109. [PubMed] [Google Scholar]
- Schifferli J. A., Didierjean L., Saurat J. H. Immunomodulatory effects of intravenous immunoglobulin G. J Rheumatol. 1991 Jun;18(6):937–939. [PubMed] [Google Scholar]
- Steinman L. The development of rational strategies for selective immunotherapy against autoimmune demyelinating disease. Adv Immunol. 1991;49:357–379. doi: 10.1016/s0065-2776(08)60779-8. [DOI] [PubMed] [Google Scholar]
- Sullivan K. M., Kopecky K. J., Jocom J., Fisher L., Buckner C. D., Meyers J. D., Counts G. W., Bowden R. A., Peterson F. B., Witherspoon R. P. Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N Engl J Med. 1990 Sep 13;323(11):705–712. doi: 10.1056/NEJM199009133231103. [DOI] [PubMed] [Google Scholar]
- Sultan Y., Kazatchkine M. D., Maisonneuve P., Nydegger U. E. Anti-idiotypic suppression of autoantibodies to factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin. Lancet. 1984 Oct 6;2(8406):765–768. doi: 10.1016/s0140-6736(84)90701-3. [DOI] [PubMed] [Google Scholar]
- Takei S., Arora Y. K., Walker S. M. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens [see comment]. J Clin Invest. 1993 Feb;91(2):602–607. doi: 10.1172/JCI116240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vassilev T., Gelin C., Kaveri S. V., Zilber M. T., Boumsell L., Kazatchkine M. D. Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg). Clin Exp Immunol. 1993 Jun;92(3):369–372. doi: 10.1111/j.1365-2249.1993.tb03407.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wacholtz M. C., Lipsky P. E. Treatment of lupus nephritis with CD5 PLUS, an immunoconjugate of an anti-CD5 monoclonal antibody and ricin A chain. Arthritis Rheum. 1992 Jul;35(7):837–839. doi: 10.1002/art.1780350721. [DOI] [PubMed] [Google Scholar]
- Waldmann H. Manipulation of T-cell responses with monoclonal antibodies. Annu Rev Immunol. 1989;7:407–444. doi: 10.1146/annurev.iy.07.040189.002203. [DOI] [PubMed] [Google Scholar]
- Wofsy D., Seaman W. E. Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med. 1985 Feb 1;161(2):378–391. doi: 10.1084/jem.161.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yadin O., Sarov B., Naggan L., Slor H., Shoenfeld Y. Natural autoantibodies in the serum of healthy women--a five-year follow-up. Clin Exp Immunol. 1989 Mar;75(3):402–406. [PMC free article] [PubMed] [Google Scholar]
- Zemmour J., Parham P. HLA class I nucleotide sequences, 1992. Immunogenetics. 1993;37(4):239–250. doi: 10.1007/BF00187449. [DOI] [PubMed] [Google Scholar]
- van Schaik I. N., Lundkvist I., Vermeulen M., Brand A. Polyvalent immunoglobulin for intravenous use interferes with cell proliferation in vitro. J Clin Immunol. 1992 Sep;12(5):325–334. doi: 10.1007/BF00920789. [DOI] [PubMed] [Google Scholar]
