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The Journal of experimental medicine1979; 149(2); 436-447; doi: 10.1084/jem.149.2.436

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Abstract: Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.
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Publication Date: 1979-02-01 PubMed ID: 84044PubMed Central: PMC2184807DOI: 10.1084/jem.149.2.436Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines how T-lymphocyte cells in mice respond to specific protein antigens, specifically cytochrome c or its fragment peptides. It discovered that the T cells could distinguish between peptides differing by only one amino acid.

Objective of the Study

  • The primary focus of this research is to understand the specifics of T-lymphocyte reactions to cytochrome c molecules and their derived peptides from distinct species. This understanding helps determine the precise immunogenicity level and the lymphocyte response to the perturbations in the antigen structure.

Methodology

  • The methodology involved the application of antigen-driven in vitro T-cell proliferation techniques. They used cytochrome c molecules, derived peptides, and reconstituted hybrid proteins from diverse species as antigenic probes. This allowed the detection of T-cell responses with high sensitivity.

Findings

  • The research identified that the T cells of primed mice could differentiate between peptide fragments differing by merely a single amino acid residue. This indicates a refined specificity in the immune response of these cells.
  • This finding was confirmed by the pattern of cross-reactivity detected in the responses to closely related cytochrome c proteins. It was also verified when artificial hybrid molecules, synthesized by covalently linking peptide fragments, were analyzed.

Implications

  • The detected pattern of T-cell specificity showed a haplotype (BDF1) dependency, suggesting a genetic influence on this fine-tuned immune response. However, similar findings about this specificity have been found in other strains, but associated with different residues. This leads to the conclusion that this refined level of T-cell immune response is a fundamental characteristic of lymphocytes, albeit potentially influenced by the host’s genetic context.

Cite This Article

APA
Corradin G, Chiller JM. (1979). Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes. J Exp Med, 149(2), 436-447. https://doi.org/10.1084/jem.149.2.436

Publication

The Journal of experimental medicine
ISSN: 0022-1007
NlmUniqueID: 2985109R
Country: United States
Language: English
Volume: 149
Issue: 2
Pages: 436-447

Researcher Affiliations

Corradin, G
    Chiller, J M

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Cattle
      • Cytochrome c Group / immunology
      • Epitopes
      • H-2 Antigens
      • Horses
      • Immunologic Memory
      • Lymph Nodes / immunology
      • Lymphocyte Activation
      • Mice
      • Peptide Fragments / immunology
      • Rabbits
      • Species Specificity
      • T-Lymphocytes / immunology

      References

      This article includes 29 references
      1. Charreire J, Faure A, Bach JF. Studies on B- and T-cell receptors for lysozyme.. Immunology 1975 Sep;29(3):423-32.
        pubmed: 1100519
      2. Eichmann K, Rajewsky K. Induction of T and B cell immunity by anti-idiotypic antibody.. Eur J Immunol 1975 Oct;5(10):661-6.
        pubmed: 11993330doi: 10.1002/eji.1830051002google scholar: lookup
      3. Swanson R, Trus BL, Mandel N, Mandel G, Kallai OB, Dickerson RE. Tuna cytochrome c at 2.0 A resolution. I. Ferricytochrome structure analysis.. J Biol Chem 1977 Jan 25;252(2):759-75.
        pubmed: 13079
      4. Mage MG, McHugh LL, Rothstein TL. 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.
        pubmed: 15036doi: 10.1016/0022-1759(77)90016-3google scholar: lookup
      5. Rosenthal AS, Barcinski MA, Blake JT. Determinant selection is a macrophage dependent immune response gene function.. Nature 1977 May 12;267(5607):156-8.
        pubmed: 16073428doi: 10.1038/267156a0google scholar: lookup
      6. Andersson LC, Aguet M, Wight E, Andersson R, Binz H, Wigzell H. Induction of specific immune unresponsiveness using purified mixed leukocyte culture-activated T lymphoblasts as autoimmunogen. I. Demonstration of general validity as to species and histocompatibility barriers.. J Exp Med 1977 Oct 1;146(4):1124-37.
        pubmed: 302312doi: 10.1084/jem.146.4.1124google scholar: lookup
      7. Hoffmann M, Kappler JW. Regulation of the immune response. II. Qualitative and quantitative differences between thymus- and bone marrow-derived lymphocytes in the recognition of antigen.. J Exp Med 1973 Mar 1;137(3):721-39.
        pubmed: 4120287doi: 10.1084/jem.137.3.721google scholar: lookup
      8. Weigle WO. Immunological unresponsiveness.. Adv Immunol 1973;16:61-122.
        pubmed: 4125922doi: 10.1016/s0065-2776(08)60296-5google scholar: lookup
      9. Shevach EM, Rosenthal AS. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response.. J Exp Med 1973 Nov 1;138(5):1213-29.
        pubmed: 4126770doi: 10.1084/jem.138.5.1213google scholar: lookup
      10. Davie JM, Paul WE. Antigen-binding receptors on lymphocytes.. Contemp Top Immunobiol 1974;3:171-92.
        pubmed: 4133996doi: 10.1007/978-1-4684-3045-5_7google scholar: lookup
      11. Fisher WR, Taniuchi H, Anfinsen CB. On the role of heme in the formation of the structure of cytochrome c.. J Biol Chem 1973 May 10;248(9):3188-95.
        pubmed: 4349479
      12. Corradin G, Harbury HA. Reconstitution of horse heart cytochrome c: reformation of the peptide bond linking residues 65 and 66.. Biochem Biophys Res Commun 1974 Dec 23;61(4):1400-6.
        pubmed: 4376012doi: 10.1016/s0006-291x(74)80439-0google scholar: lookup
      13. Julius MH, Simpson E, Herzenberg LA. A rapid method for the isolation of functional thymus-derived murine lymphocytes.. Eur J Immunol 1973 Oct;3(10):645-9.
        pubmed: 4587740doi: 10.1002/eji.1830031011google scholar: lookup
      14. Reichlin M. Amino acid substitution and the antigenicity of globular proteins.. Adv Immunol 1975;20:71-123.
        pubmed: 47221doi: 10.1016/s0065-2776(08)60207-2google scholar: lookup
      15. Sela M. Antigenicity: some molecular aspects.. Science 1969 Dec 12;166(3911):1365-74.
        pubmed: 4900368doi: 10.1126/science.166.3911.1365google scholar: lookup
      16. Schwartz RH, Jackson L, Paul WE. T lymphocyte-enriched murine peritoneal exudate cells. I. A reliable assay for antigen-induced T lymphocyte proliferation.. J Immunol 1975 Nov;115(5):1330-8.
        pubmed: 51890
      17. Corradin G, Harbury HA. Reconstitution of horse heart cytochrome c: interaction of the components obtained upon cleavage of the peptide bond following methionine residue 65.. Proc Natl Acad Sci U S A 1971 Dec;68(12):3036-9.
        pubmed: 5289248doi: 10.1073/pnas.68.12.3036google scholar: lookup
      18. Takatsu K, Ishizaka K. Reaginic antibody formation in the mouse. VI. Suppression of IgE and IgG antibody responses to ovalbumin following the administration of high dose urea-denatured antigen.. Cell Immunol 1975 Dec;20(2):276-89.
        pubmed: 54223doi: 10.1016/0008-8749(75)90105-7google scholar: lookup
      19. Corradin G, Harbury HA. Cleavage of cytochrome c with cyanogen bromide.. Biochim Biophys Acta 1970 Dec 22;221(3):489-96.
        pubmed: 5499432doi: 10.1016/0005-2795(70)90219-9google scholar: lookup
      20. Janeway CA, Paul WE. The specificity of cellular immune responses in guinea pigs. III. The precision of antigen recognition by T lymphocytes.. J Exp Med 1976 Dec 1;144(6):1641-56.
        pubmed: 63531doi: 10.1084/jem.144.6.1641google scholar: lookup
      21. Stashenko PP, Schlossman SF. Antigen recognition: the specificity of an isolated T lymphocyte population.. J Immunol 1977 Feb;118(2):544-50.
        pubmed: 65426
      22. Urbanski GJ, Margoliash E. Topographic determinants on cytochrome c. I. The complete antigenic structures of rabbit, mouse, and guanaco cytochromes c in rabbits and mice1.. J Immunol 1977 Apr;118(4):1170-80.
        pubmed: 66279
      23. Binz H, Wigzell H. Antigen-binding, idiotypic T-lymphocyte receptors.. Contemp Top Immunobiol 1977;7:113-77.
        pubmed: 69514doi: 10.1007/978-1-4684-3054-7_4google scholar: lookup
      24. Rajewsky K, Eichmann K. Antigen receptors of T helper cells.. Contemp Top Immunobiol 1977;7:69-112.
        pubmed: 69518doi: 10.1007/978-1-4684-3054-7_3google scholar: lookup
      25. Corradin G, Etlinger HM, Chiller JM. Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice.. J Immunol 1977 Sep;119(3):1048-53.
        pubmed: 70468
      26. Sercarz EE, Yowell RL, Turkin D, Miller A, Araneo BA, Adorini L. Different functional specificity repertoires for suppressor and helper T cells.. Immunol Rev 1978;39:108-36.
        pubmed: 75167doi: 10.1111/j.1600-065x.1978.tb00398.xgoogle scholar: lookup
      27. 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):1809-12.
        pubmed: 77879
      28. Wolff ML, Reichlin M. Antigenic specificity of T cell receptors for cytochrome C on guinea pig lymphocytes.. Immunochemistry 1978 May;15(5):289-94.
        pubmed: 81170doi: 10.1016/0161-5890(78)90087-1google scholar: lookup
      29. Barcinski MA, Rosenthal AS. Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells.. J Exp Med 1977 Mar 1;145(3):726-42.
        pubmed: 95787doi: 10.1084/jem.145.3.726google scholar: lookup

      Citations

      This article has been cited 21 times.
      1. Coscolla M, Copin R, Sutherland J, Gehre F, de Jong B, Owolabi O, Mbayo G, Giardina F, Ernst JD, Gagneux S. M. tuberculosis T Cell Epitope Analysis Reveals Paucity of Antigenic Variation and Identifies Rare Variable TB Antigens. Cell Host Microbe 2015 Nov 11;18(5):538-48.
        doi: 10.1016/j.chom.2015.10.008pubmed: 26607161google scholar: lookup
      2. Clayberger C, Dekruyff RH, Aisenberg J, Cantor H. Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells. J Exp Med 1983 Jun 1;157(6):1906-19.
        doi: 10.1084/jem.157.6.1906pubmed: 6602202google scholar: lookup
      3. Sadegh-Nasseri S, Kipp DE, Taylor BA, Miller A, Sercarz E. Selective reversal of H-2 linked genetic unresponsiveness to lysozymes. I. Non-H-2 gene(s) closely linked to the Ir-2 locus on chromosome 2 permit(s) an antilysozyme response in H-2b mice. Immunogenetics 1984;20(5):535-46.
        doi: 10.1007/BF00364356pubmed: 6437975google scholar: lookup
      4. Hackett CJ, Dietzschold B, Gerhard W, Ghrist B, Knorr R, Gillessen D, Melchers F. Influenza virus site recognized by a murine helper T cell specific for H1 strains. Localization to a nine amino acid sequence in the hemagglutinin molecule. J Exp Med 1983 Aug 1;158(2):294-302.
        doi: 10.1084/jem.158.2.294pubmed: 6224879google scholar: lookup
      5. Milich DR, Leroux-Roels GG, Louie RE, Chisari FV. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). IV. Distinct H-2-linked Ir genes control antibody responses to different HBsAg determinants on the same molecule and map to the I-A and I-C subregions. J Exp Med 1984 Jan 1;159(1):41-56.
        doi: 10.1084/jem.159.1.41pubmed: 6198427google scholar: lookup
      6. Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex. J Exp Med 1983 Feb 1;157(2):705-19.
        doi: 10.1084/jem.157.2.705pubmed: 6185617google scholar: lookup
      7. Weaver M, Singhai R, Sikora L, Levy JG. Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects. J Exp Med 1983 Jan 1;157(1):285-300.
        doi: 10.1084/jem.157.1.285pubmed: 6184440google scholar: lookup
      8. Berkower I, Buckenmeyer GK, Gurd FR, Berzofsky JA. A possible immunodominant epitope recognized by murine T lymphocytes immune to different myoglobins. Proc Natl Acad Sci U S A 1982 Aug;79(15):4723-7.
        doi: 10.1073/pnas.79.15.4723pubmed: 6181511google scholar: lookup
      9. Thomas DW, Hsieh KH, Schauster JL, Mudd MS, Wilner GD. Nature of T lymphocyte recognition of macrophage-associated antigens. V. Contribution of individual peptide residues of human fibrinopeptide B to T lymphocyte responses. J Exp Med 1980 Sep 1;152(3):620-32.
        doi: 10.1084/jem.152.3.620pubmed: 6157771google scholar: lookup
      10. Mathieu-Mahul D, Chen LK, Larsen CJ, Bensussan A. Detection of T cell receptor alpha chain locus rearrangements in human antigen-specific T lymphocyte clones using a DNA probe specific for chromosome region 14q11. J Exp Med 1986 May 1;163(5):1308-13.
        doi: 10.1084/jem.163.5.1308pubmed: 3486246google scholar: lookup
      11. Morrison LA, Lukacher AE, Braciale VL, Fan DP, Braciale TJ. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med 1986 Apr 1;163(4):903-21.
        doi: 10.1084/jem.163.4.903pubmed: 3485173google scholar: lookup
      12. Maryanski JL, Pala P, Cerottini JC, Corradin G. Synthetic peptides as antigens and competitors in recognition by H-2-restricted cytolytic T cells specific for HLA. J Exp Med 1988 Apr 1;167(4):1391-405.
        doi: 10.1084/jem.167.4.1391pubmed: 3128632google scholar: lookup
      13. Eisenlohr LC, Gerhard W, Hackett CJ. Role of receptor-binding activity of the viral hemagglutinin molecule in the presentation of influenza virus antigens to helper T cells. J Virol 1987 May;61(5):1375-83.
        doi: 10.1128/JVI.61.5.1375-1383.1987pubmed: 2952806google scholar: lookup
      14. Schneck J, Munitz T, Coligan JE, Maloy WL, Margulies DH, Singer A. Inhibition of allorecognition by an H-2Kb-derived peptide is evidence for a T-cell binding region on a major histocompatibility complex molecule. Proc Natl Acad Sci U S A 1989 Nov;86(21):8516-20.
        doi: 10.1073/pnas.86.21.8516pubmed: 2813409google scholar: lookup
      15. Sweetser MT, Braciale VL, Braciale TJ. Class I major histocompatibility complex-restricted T lymphocyte recognition of the influenza hemagglutinin. Overlap between class I cytotoxic T lymphocytes and antibody sites. J Exp Med 1989 Oct 1;170(4):1357-68.
        doi: 10.1084/jem.170.4.1357pubmed: 2477491google scholar: lookup
      16. Chimini G, Pala P, Sire J, Jordan BR, Maryanski JL. Recognition of oligonucleotide-encoded T cell epitopes introduced into a gene unrelated to the original antigen. J Exp Med 1989 Jan 1;169(1):297-302.
        doi: 10.1084/jem.169.1.297pubmed: 2462610google scholar: lookup
      17. Heber-Katz E, Valentine S, Dietzschold B, Burns-Purzycki C. Overlapping T cell antigenic sites on a synthetic peptide fragment from herpes simplex virus glycoprotein D, the degenerate MHC restriction elicited, and functional evidence for antigen-Ia interaction. J Exp Med 1988 Feb 1;167(2):275-87.
        doi: 10.1084/jem.167.2.275pubmed: 2450157google scholar: lookup
      18. Acuto O, Fabbi M, Bensussan A, Milanese C, Campen TJ, Royer HD, Reinherz EL. The human T-cell receptor. J Clin Immunol 1985 May;5(3):141-57.
        doi: 10.1007/BF00915505pubmed: 2409103google scholar: lookup
      19. Puré E, Inaba K, Crowley MT, Tardelli L, Witmer-Pack MD, Ruberti G, Fathman G, Steinman RM. Antigen processing by epidermal Langerhans cells correlates with the level of biosynthesis of major histocompatibility complex class II molecules and expression of invariant chain. J Exp Med 1990 Nov 1;172(5):1459-69.
        doi: 10.1084/jem.172.5.1459pubmed: 2121888google scholar: lookup
      20. Solinger AM, Ultee ME, Margoliash E, Schwartz RH. T-lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two complementing major histocompatibility complex-linked immune response genes. J Exp Med 1979 Oct 1;150(4):830-48.
        doi: 10.1084/jem.150.4.830pubmed: 92520google scholar: lookup
      21. Berzofsky JA, Richman LK, Killion DJ. Distinct H-2-linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin. Proc Natl Acad Sci U S A 1979 Aug;76(8):4046-50.
        doi: 10.1073/pnas.76.8.4046pubmed: 91172google scholar: lookup
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