Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1993 Jan 1;177(1):119–125. doi: 10.1084/jem.177.1.119

Antigen recognition properties of mutant V beta 3+ T cell receptors are consistent with an immunoglobulin-like structure for the receptor

PMCID: PMC2190864  PMID: 8380294

Abstract

We examined the effect of mutations in the V beta portion of a pigeon cytochrome c (cyto c)-specific V beta 3+/V alpha 11+ T cell receptor on its ability to recognize cyto c/IEk and various superantigens. The results were consistent with an immunoglobulin-like structure for the receptor V beta domain and with separate interaction sites on V beta for conventional antigen and superantigens. An amino acid predicted to lie in CDR1 was critical for cyto c/IEk but not superantigen recognition, while several amino acids predicted to lie in the hypervariable region 4 loop were critical for superantigen but not cyto c/IEk recognition.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Arnold L. W., Grdina T. A., Whitmore A. C., Haughton G. Ig isotype switching in B lymphocytes. Isolation and characterization of clonal variants of the murine Ly-1+ B cell lymphoma, CH12, expressing isotypes other than IgM. J Immunol. 1988 Jun 15;140(12):4355–4363. [PubMed] [Google Scholar]
  2. Burgert H. G., White J., Weltzien H. U., Marrack P., Kappler J. W. Reactivity of V beta 17a+ CD8+ T cell hybrids. Analysis using a new CD8+ T cell fusion partner. J Exp Med. 1989 Dec 1;170(6):1887–1904. doi: 10.1084/jem.170.6.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Callahan J. E., Herman A., Kappler J. W., Marrack P. Stimulation of B10.BR T cells with superantigenic staphylococcal toxins. J Immunol. 1990 Apr 1;144(7):2473–2479. [PubMed] [Google Scholar]
  4. Cazenave P. A., Marche P. N., Jouvin-Marche E., Voegtlé D., Bonhomme F., Bandeira A., Coutinho A. V beta 17 gene polymorphism in wild-derived mouse strains: two amino acid substitutions in the V beta 17 region greatly alter T cell receptor specificity. Cell. 1990 Nov 16;63(4):717–728. doi: 10.1016/0092-8674(90)90138-5. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Choi Y. W., Kotzin B., Herron L., Callahan J., Marrack P., Kappler J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8941–8945. doi: 10.1073/pnas.86.22.8941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chou H. S., Nelson C. A., Godambe S. A., Chaplin D. D., Loh D. Y. Germline organization of the murine T cell receptor beta-chain genes. Science. 1987 Oct 23;238(4826):545–548. doi: 10.1126/science.2821625. [DOI] [PubMed] [Google Scholar]
  10. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  11. Dellabona P., Peccoud J., Kappler J., Marrack P., Benoist C., Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove. Cell. 1990 Sep 21;62(6):1115–1121. doi: 10.1016/0092-8674(90)90388-u. [DOI] [PubMed] [Google Scholar]
  12. Engel I., Hedrick S. M. Site-directed mutations in the VDJ junctional region of a T cell receptor beta chain cause changes in antigenic peptide recognition. Cell. 1988 Aug 12;54(4):473–484. doi: 10.1016/0092-8674(88)90068-2. [DOI] [PubMed] [Google Scholar]
  13. Fink P. J., Matis L. A., McElligott D. L., Bookman M., Hedrick S. M. Correlations between T-cell specificity and the structure of the antigen receptor. Nature. 1986 May 15;321(6067):219–226. doi: 10.1038/321219a0. [DOI] [PubMed] [Google Scholar]
  14. Fischer H., Dohlsten M., Lindvall M., Sjögren H. O., Carlsson R. Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines. J Immunol. 1989 May 1;142(9):3151–3157. [PubMed] [Google Scholar]
  15. Fischmann T. O., Bentley G. A., Bhat T. N., Boulot G., Mariuzza R. A., Phillips S. E., Tello D., Poljak R. J. Crystallographic refinement of the three-dimensional structure of the FabD1.3-lysozyme complex at 2.5-A resolution. J Biol Chem. 1991 Jul 15;266(20):12915–12920. [PubMed] [Google Scholar]
  16. Fleischer B., Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med. 1988 May 1;167(5):1697–1707. doi: 10.1084/jem.167.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fry A. M., Cotterman M. M., Matis L. A. The influence of self-MHC and non-MHC antigens on the selection of an antigen-specific T cell receptor repertoire. J Immunol. 1989 Oct 15;143(8):2723–2729. [PubMed] [Google Scholar]
  18. Fry A. M., Matis L. A. Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response. Nature. 1988 Oct 27;335(6193):830–832. doi: 10.1038/335830a0. [DOI] [PubMed] [Google Scholar]
  19. Gahm S. J., Fowlkes B. J., Jameson S. C., Gascoigne N. R., Cotterman M. M., Kanagawa O., Schwartz R. H., Matis L. A. Profound alteration in an alpha beta T-cell antigen receptor repertoire due to polymorphism in the first complementarity-determining region of the beta chain. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10267–10271. doi: 10.1073/pnas.88.22.10267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Griffith I. J., Nabavi N., Ghogawala Z., Chase C. G., Rodriguez M., McKean D. J., Glimcher L. H. Structural mutation affecting intracellular transport and cell surface expression of murine class II molecules. J Exp Med. 1988 Feb 1;167(2):541–555. doi: 10.1084/jem.167.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Herman A., Croteau G., Sekaly R. P., Kappler J., Marrack P. HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J Exp Med. 1990 Sep 1;172(3):709–717. doi: 10.1084/jem.172.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Herman A., Kappler J. W., Marrack P., Pullen A. M. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol. 1991;9:745–772. doi: 10.1146/annurev.iy.09.040191.003525. [DOI] [PubMed] [Google Scholar]
  23. Jameson S. C., Nakajima P. B., Brooks J. L., Heath W., Kanagawa O., Gascoigne N. R. The T cell receptor V alpha 11 gene family. Analysis of allelic sequence polymorphism and demonstration of J alpha region-dependent recognition by allele-specific antibodies. J Immunol. 1991 Nov 1;147(9):3185–3193. [PubMed] [Google Scholar]
  24. Jorgensen J. L., Esser U., Fazekas de St Groth B., Reay P. A., Davis M. M. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature. 1992 Jan 16;355(6357):224–230. doi: 10.1038/355224a0. [DOI] [PubMed] [Google Scholar]
  25. Jorgensen J. L., Reay P. A., Ehrich E. W., Davis M. M. Molecular components of T-cell recognition. Annu Rev Immunol. 1992;10:835–873. doi: 10.1146/annurev.iy.10.040192.004155. [DOI] [PubMed] [Google Scholar]
  26. Kappler J. W., Herman A., Clements J., Marrack P. Mutations defining functional regions of the superantigen staphylococcal enterotoxin B. J Exp Med. 1992 Feb 1;175(2):387–396. doi: 10.1084/jem.175.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kappler J. W., Skidmore B., White J., Marrack P. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med. 1981 May 1;153(5):1198–1214. doi: 10.1084/jem.153.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kappler J. W., Wade T., White J., Kushnir E., Blackman M., Bill J., Roehm N., Marrack P. A T cell receptor V beta segment that imparts reactivity to a class II major histocompatibility complex product. Cell. 1987 Apr 24;49(2):263–271. doi: 10.1016/0092-8674(87)90567-8. [DOI] [PubMed] [Google Scholar]
  29. Kaye J., Janeway C. A., Jr The alpha- and beta-subunits of a murine T cell antigen/Ia receptor have a molecular weight of 31,000 in the absence of N-linked glycosylation. J Immunol. 1984 Nov;133(5):2291–2293. [PubMed] [Google Scholar]
  30. King L. B., Lund F. E., White D. A., Sharma S., Corley R. B. Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9. J Immunol. 1990 Apr 15;144(8):3218–3227. [PubMed] [Google Scholar]
  31. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  32. Lascombe M. B., Alzari P. M., Boulot G., Saludjian P., Tougard P., Berek C., Haba S., Rosen E. M., Nisonoff A., Poljak R. J. Three-dimensional structure of Fab R19.9, a monoclonal murine antibody specific for the p-azobenzenearsonate group. Proc Natl Acad Sci U S A. 1989 Jan;86(2):607–611. doi: 10.1073/pnas.86.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Marquart M., Deisenhofer J., Huber R., Palm W. Crystallographic refinement and atomic models of the intact immunoglobulin molecule Kol and its antigen-binding fragment at 3.0 A and 1.0 A resolution. J Mol Biol. 1980 Aug 25;141(4):369–391. doi: 10.1016/0022-2836(80)90252-1. [DOI] [PubMed] [Google Scholar]
  34. Marrack P., Kappler J. T cells can distinguish between allogeneic major histocompatibility complex products on different cell types. Nature. 1988 Apr 28;332(6167):840–843. doi: 10.1038/332840a0. [DOI] [PubMed] [Google Scholar]
  35. McIntyre B. W., Allison J. P. Biosynthesis and processing of murine T-cell antigen receptor. Cell. 1984 Oct;38(3):659–665. doi: 10.1016/0092-8674(84)90260-5. [DOI] [PubMed] [Google Scholar]
  36. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  37. Nalefski E. A., Wong J. G., Rao A. Amino acid substitutions in the first complementarity-determining region of a murine T-cell receptor alpha chain affect antigen-major histocompatibility complex recognition. J Biol Chem. 1990 May 25;265(15):8842–8846. [PubMed] [Google Scholar]
  38. Nicolas J. F., Wegmann D., Lebrun P., Kaiserlian D., Tovey J., Glasebrook A. L. Relationship of B cell Fc receptors to T cell recognition of Mls antigen. Eur J Immunol. 1987 Nov;17(11):1561–1565. doi: 10.1002/eji.1830171106. [DOI] [PubMed] [Google Scholar]
  39. Padlan E. A., Silverton E. W., Sheriff S., Cohen G. H., Smith-Gill S. J., Davies D. R. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5938–5942. doi: 10.1073/pnas.86.15.5938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pullen A. M., Bill J., Kubo R. T., Marrack P., Kappler J. W. Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. J Exp Med. 1991 May 1;173(5):1183–1192. doi: 10.1084/jem.173.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  42. Pullen A. M., Wade T., Marrack P., Kappler J. W. Identification of the region of T cell receptor beta chain that interacts with the self-superantigen MIs-1a. Cell. 1990 Jun 29;61(7):1365–1374. doi: 10.1016/0092-8674(90)90700-o. [DOI] [PubMed] [Google Scholar]
  43. Ronchese F., Schwartz R. H., Germain R. N. Functionally distinct subsites on a class II major histocompatibility complex molecule. Nature. 1987 Sep 17;329(6136):254–256. doi: 10.1038/329254a0. [DOI] [PubMed] [Google Scholar]
  44. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  45. Schiffer M., Wu T. T., Kabat E. A. Subgroups of variable region genes of beta chains of T-cell receptors for antigen. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4461–4463. doi: 10.1073/pnas.83.12.4461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sheriff S., Silverton E. W., Padlan E. A., Cohen G. H., Smith-Gill S. J., Finzel B. C., Davies D. R. Three-dimensional structure of an antibody-antigen complex. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8075–8079. doi: 10.1073/pnas.84.22.8075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Siu G., Clark S. P., Yoshikai Y., Malissen M., Yanagi Y., Strauss E., Mak T. W., Hood L. The human T cell antigen receptor is encoded by variable, diversity, and joining gene segments that rearrange to generate a complete V gene. Cell. 1984 Jun;37(2):393–401. doi: 10.1016/0092-8674(84)90369-6. [DOI] [PubMed] [Google Scholar]
  48. Sorger S. B., Hedrick S. M., Fink P. J., Bookman M. A., Matis L. A. Generation of diversity in T cell receptor repertoire specific for pigeon cytochrome c. J Exp Med. 1987 Feb 1;165(2):279–301. doi: 10.1084/jem.165.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Winoto A., Mjolsness S., Hood L. Genomic organization of the genes encoding mouse T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):832–836. doi: 10.1038/316832a0. [DOI] [PubMed] [Google Scholar]
  50. Winoto A., Urban J. L., Lan N. C., Goverman J., Hood L., Hansburg D. Predominant use of a V alpha gene segment in mouse T-cell receptors for cytochrome c. Nature. 1986 Dec 18;324(6098):679–682. doi: 10.1038/324679a0. [DOI] [PubMed] [Google Scholar]
  51. Woodland D. L., Happ M. P., Gollob K. J., Palmer E. An endogenous retrovirus mediating deletion of alpha beta T cells? Nature. 1991 Feb 7;349(6309):529–530. doi: 10.1038/349529a0. [DOI] [PubMed] [Google Scholar]
  52. Woodland D. L., Lund F. E., Happ M. P., Blackman M. A., Palmer E., Corley R. B. Endogenous superantigen expression is controlled by mouse mammary tumor proviral loci. J Exp Med. 1991 Nov 1;174(5):1255–1258. doi: 10.1084/jem.174.5.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES