Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1986 Mar;57(3):331–335.

Influence of antigen structure on the activation and induction of unresponsiveness in cloned human T lymphocytes.

J R Lamb, M Feldmann, N Green, R A Lerner
PMCID: PMC1453820  PMID: 2420700

Abstract

Using cloned human helper T lymphocytes reactive with a 24 amino acid peptide (p20) of the carboxyl terminal of the HA-1 molecule of influenza haemagglutinin we have investigated the influence of antigen structure on the activation and in the induction of antigen specific unresponsiveness of T cells. For this analysis stereoisomers and structural isomers of p20 have been constructed. P20 in the form of a single loop created by a disulphide based between residue 306 and an additional cysteine at position 330 was able to activate the helper T cells in the presence of accessory cells but unable to induce tolerance. This result suggested that critical residues were prevented from direct interaction with the T-cell receptor and/or the MHC Class II determinants and required processing to expose them. The enantiomer (D-p20) and the inverted sequence (retro-L-p20) which have non complementary side chain topography as compared to the parent peptide neither activated nor tolerized the T cells. Furthermore the retro-D-p20 isomer which has the same side chain topography as L-p20 but with a reversal of amino and carboxyl acid groups also failed to stimulate or tolerize. Therefore T-cell antigen recognition is not determined by side chains alone. The results presented suggest that structure of extrinsic antigen influences T-cell antigen recognition.

Full text

PDF
331

Selected References

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

  1. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  2. Bergholtz B. O., Thorsby E. HLA-D restriction of the macrophage-dependent response of immune human T lymphocytes to PPD in vitro: inhibition by anti-HLA-DR antisera. Scand J Immunol. 1978;8(1):63–73. doi: 10.1111/j.1365-3083.1978.tb00496.x. [DOI] [PubMed] [Google Scholar]
  3. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  4. Green N., Alexander H., Olson A., Alexander S., Shinnick T. M., Sutcliffe J. G., Lerner R. A. Immunogenic structure of the influenza virus hemagglutinin. Cell. 1982 Mar;28(3):477–487. doi: 10.1016/0092-8674(82)90202-1. [DOI] [PubMed] [Google Scholar]
  5. Jou W. M., Verhoeyen M., Devos R., Saman E., Fang R., Huylebroeck D., Fiers W., Threlfall G., Barber C., Carey N. Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell. 1980 Mar;19(3):683–696. doi: 10.1016/s0092-8674(80)80045-6. [DOI] [PubMed] [Google Scholar]
  6. Kronenberg M., Goverman J., Haars R., Malissen M., Kraig E., Phillips L., Delovitch T., Suciu-Foca N., Hood L. Rearrangement and transcription of the beta-chain genes of the T-cell antigen receptor in different types of murine lymphocytes. Nature. 1985 Feb 21;313(6004):647–653. doi: 10.1038/313647a0. [DOI] [PubMed] [Google Scholar]
  7. Lamb J. R., Eckels D. D., Lake P., Woody J. N., Green N. Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin. Nature. 1982 Nov 4;300(5887):66–69. doi: 10.1038/300066a0. [DOI] [PubMed] [Google Scholar]
  8. Lamb J. R., Feldmann M. Essential requirement for major histocompatibility complex recognition in T-cell tolerance induction. Nature. 1984 Mar 1;308(5954):72–74. doi: 10.1038/308072a0. [DOI] [PubMed] [Google Scholar]
  9. Matis L. A., Longo D. L., Hedrick S. M., Hannum C., Margoliash E., Schwartz R. H. Clonal analysis of the major histocompatibility complex restriction and the fine specificity of antigen recognition in the T cell proliferative response to cytochrome C. J Immunol. 1983 Apr;130(4):1527–1535. [PubMed] [Google Scholar]
  10. Rosenthal A. S., Shevach E. M. Function of macrophages in antigen recognition by guinea pig T lymphocytes. I. Requirement for histocompatible macrophages and lymphocytes. J Exp Med. 1973 Nov 1;138(5):1194–1212. doi: 10.1084/jem.138.5.1194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Schirrmacher V., Wigzell H. Immune responses against native and chemically modified albumins in mice. II. Effect of electric charge and conformation on the humoral antibody response and on helper T cell responses. J Immunol. 1974 Nov;113(5):1635–1643. [PubMed] [Google Scholar]
  12. Thomas D. W., Hoffman M. D., Wilner G. D. T lymphocyte recognition of peptide antigens: evidence favoring the formation of neoantigenic determinants. J Exp Med. 1982 Jul 1;156(1):289–293. doi: 10.1084/jem.156.1.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Thomas D. W., Hsieh K. H., Schauster J. L., Wilner G. D. Fine specificity of genetic regulation of guinea pig T lymphocyte responses to angiotensin II and related peptides. J Exp Med. 1981 Mar 1;153(3):583–594. doi: 10.1084/jem.153.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Unanue E. R. Antigen-presenting function of the macrophage. Annu Rev Immunol. 1984;2:395–428. doi: 10.1146/annurev.iy.02.040184.002143. [DOI] [PubMed] [Google Scholar]
  15. Zanders E. D., Feldmann M., Green N., Lamb J. R. Direct evaluation of antigen binding to human T lymphocyte clones: involvement of major histocompatibility complex products in antigen binding. Eur J Immunol. 1984 Dec;14(12):1101–1105. doi: 10.1002/eji.1830141207. [DOI] [PubMed] [Google Scholar]
  16. Ziegler H. K., Unanue E. R. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. Proc Natl Acad Sci U S A. 1982 Jan;79(1):175–178. doi: 10.1073/pnas.79.1.175. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES