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. 1988 Apr;85(8):2728–2732. doi: 10.1073/pnas.85.8.2728

Allorecognition of purified major histocompatibility complex glycoproteins by cytotoxic T lymphocytes.

T J Elliott 1, H N Eisen 1
PMCID: PMC280072  PMID: 2451830

Abstract

To investigate how T cells recognize allogeneic class I proteins encoded by the major histocompatibility complex (MHC), we examined the human cytotoxic T lymphocytes (CTL) elicited in a mixed lymphocyte reaction against a lymphoblastoid B-cell line (JY) whose MHC-class I proteins are HLA-A2 and -B7. By panning the responding T cells on plates that were coated with purified HLA-A2, an essentially pure population of CD8+ anti-HLA-A2 CTL was isolated in a single step and established as a cell line designated A2p. In addition to lysing HLA-A2+ target cells, the A2p cells lysed HLA-A2- cells, including mouse cells (P815), when purified native HLA-A2 was attached to them, but not when denatured HLA-A2 was attached. Thus, contrary to the general rule that T cells recognize sequential antigenic determinants in denatured protein antigens, the alloreactive CTLs appear to recognize determinants that depend upon the native configuration of HLA-A2; however, the possibility that these T cells recognize a peptide adduct persistently associated with purified, soluble HLA-A2 has not been ruled out.

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Selected References

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

  1. Acuto O., Campen T. J., Royer H. D., Hussey R. E., Poole C. B., Reinherz E. L. Molecular analysis of T cell receptor (Ti) variable region (V) gene expression. Evidence that a single Ti beta V gene family can be used in formation of V domains on phenotypically and functionally diverse T cell populations. J Exp Med. 1985 Jun 1;161(6):1326–1343. doi: 10.1084/jem.161.6.1326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bigler R. D., Posnett D. N., Chiorazzi N. Stimulation of a subset of normal resting T lymphocytes by a monoclonal antibody to a crossreactive determinant of the human T cell antigen receptor. J Exp Med. 1985 Jun 1;161(6):1450–1463. doi: 10.1084/jem.161.6.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brooks C. G., Holscher M., Urdal D. Natural killer activity in cloned cytotoxic T lymphocytes: regulation by interleukin 2, interferon, and specific antigen. J Immunol. 1985 Aug;135(2):1145–1152. [PubMed] [Google Scholar]
  5. Burns G. F., Triglia T., Werkmeister J. A. Cloned human cytotoxic T lymphocytes develop anomalous killer cell function. Clin Exp Immunol. 1986 Dec;66(3):558–565. [PMC free article] [PubMed] [Google Scholar]
  6. Elliott T. J., Glennie M. J., McBride H. M., Stevenson G. T. Analysis of the interaction of antibodies with immunoglobulin idiotypes on neoplastic B lymphocytes: implications for immunotherapy. J Immunol. 1987 Feb 1;138(3):981–988. [PubMed] [Google Scholar]
  7. Kranz D. M., Tonegawa S., Eisen H. N. Attachment of an anti-receptor antibody to non-target cells renders them susceptible to lysis by a clone of cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7922–7926. doi: 10.1073/pnas.81.24.7922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Mage M. G., McHugh L. L., Rothstein T. L. Mouse lymphocytes with and without surface immunoglobulin: preparative scale separation in polystyrene tissue culture dishes coated with specifically purified anti-immunoglobulin. J Immunol Methods. 1977;15(1):47–56. doi: 10.1016/0022-1759(77)90016-3. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Parham P., Clayberger C., Zorn S. L., Ludwig D. S., Schoolnik G. K., Krensky A. M. Inhibition of alloreactive cytotoxic T lymphocytes by peptides from the alpha 2 domain of HLA-A2. Nature. 1987 Feb 12;325(6105):625–628. doi: 10.1038/325625a0. [DOI] [PubMed] [Google Scholar]
  11. Salter R. D., Clayberger C., Lomen C. E., Krensky A. M., Parham P. In vitro mutagenesis at a single residue introduces B and T cell epitopes into a class I HLA molecule. J Exp Med. 1987 Jul 1;166(1):283–288. doi: 10.1084/jem.166.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Santos-Aguado J., Biro P. A., Fuhrmann U., Strominger J. L., Barbosa J. A. Amino acid sequences in the alpha 1 domain and not glycosylation are important in HLA-A2/beta 2-microglobulin association and cell surface expression. Mol Cell Biol. 1987 Mar;7(3):982–990. doi: 10.1128/mcb.7.3.982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ways J. P., Parham P. The binding of monoclonal antibodies to cell-surface molecules. A quantitative analysis with immunoglobulin G against two alloantigenic determinants of the human transplantation antigen HLA-A2. Biochem J. 1983 Nov 15;216(2):423–432. doi: 10.1042/bj2160423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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