Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1995 May;69(5):3134–3146. doi: 10.1128/jvi.69.5.3134-3146.1995

Functional analysis of amino acid residues encompassing and surrounding two neighboring H-2Db-restricted cytotoxic T-lymphocyte epitopes in simian virus 40 tumor antigen.

J D Lippolis 1, L M Mylin 1, D T Simmons 1, S S Tevethia 1
PMCID: PMC189015  PMID: 7535867

Abstract

Simian virus 40 tumor (T) antigen contains three H-2Db-and one H-2Kb-restricted cytotoxic T lymphocyte (CTL) epitopes (sites). Two of the H-2Db-restricted CTL epitopes, I and II/III, are separated by 7 amino acids in the amino-terminal one third of T antigen. In this study, we determine if the amino acids separating these two H-2Db-restricted CTL epitopes are dispensable for efficient processing and presentation. In addition, the importance of amino acid residues lying within and flanking the H-2Db-restricted epitopes I and II/III for efficient processing, presentation, and recognition by site-specific CTL clones was determined by using T-antigen mutants containing single-amino-acid substitutions between residues 200 and 239. Using synthetic peptides in CTL lysis and major histocompatibility complex class I stabilization assays, CTL recognition site I has been redefined to include residues 206 to 215. Substitutions in amino acids flanking either site I or site II/III did not affect recognition by any of the T-antigen-specific CTL clones. Additionally, the removal of the 7 residues separating site I and site II/III did not affect CTL recognition, thus demonstrating that these two epitopes when arranged in tandem in the native T antigen can be efficiently processed and presented to CTL clones. Differences in fine specificities of two CTL clones which recognize the same epitope (Y-1 and K-11 for site I and Y-2 and Y-3 for site II/III) have been used in conjunction with synthetic peptide variants to assign roles for residues within epitopes I and II/III with respect to TCR recognition and/or peptide-major histocompatibility complex association.

Full Text

The Full Text of this article is available as a PDF (452.5 KB).

Selected References

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

  1. Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
  2. Aki M., Shimbara N., Takashina M., Akiyama K., Kagawa S., Tamura T., Tanahashi N., Yoshimura T., Tanaka K., Ichihara A. Interferon-gamma induces different subunit organizations and functional diversity of proteasomes. J Biochem. 1994 Feb;115(2):257–269. doi: 10.1093/oxfordjournals.jbchem.a124327. [DOI] [PubMed] [Google Scholar]
  3. Akiyama K., Yokota K., Kagawa S., Shimbara N., Tamura T., Akioka H., Nothwang H. G., Noda C., Tanaka K., Ichihara A. cDNA cloning and interferon gamma down-regulation of proteasomal subunits X and Y. Science. 1994 Aug 26;265(5176):1231–1234. doi: 10.1126/science.8066462. [DOI] [PubMed] [Google Scholar]
  4. Allen P. M., Matsueda G. R., Evans R. J., Dunbar J. B., Jr, Marshall G. R., Unanue E. R. Identification of the T-cell and Ia contact residues of a T-cell antigenic epitope. 1987 Jun 25-Jul 1Nature. 327(6124):713–715. doi: 10.1038/327713a0. [DOI] [PubMed] [Google Scholar]
  5. Alsheikhly A. R. Interaction of in vitro- and in vivo-generated cytotoxic T cells with SV40 T antigen: analysis with synthetic peptides. Scand J Immunol. 1994 May;39(5):467–479. doi: 10.1111/j.1365-3083.1994.tb03402.x. [DOI] [PubMed] [Google Scholar]
  6. Anderson K., Cresswell P., Gammon M., Hermes J., Williamson A., Zweerink H. Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis. J Exp Med. 1991 Aug 1;174(2):489–492. doi: 10.1084/jem.174.2.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Anderson R. W., Tevethia M. J., Kalderon D., Smith A. E., Tevethia S. S. Fine mapping two distinct antigenic sites on simian virus 40 (SV40) T antigen reactive with SV40-specific cytotoxic T-cell clones by using SV40 deletion mutants. J Virol. 1988 Jan;62(1):285–296. doi: 10.1128/jvi.62.1.285-296.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bastin J., Rothbard J., Davey J., Jones I., Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. doi: 10.1084/jem.165.6.1508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bergmann C. C., Tong L., Cua R., Sensintaffar J., Stohlman S. Differential effects of flanking residues on presentation of epitopes from chimeric peptides. J Virol. 1994 Aug;68(8):5306–5310. doi: 10.1128/jvi.68.8.5306-5310.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Boes B., Hengel H., Ruppert T., Multhaup G., Koszinowski U. H., Kloetzel P. M. Interferon gamma stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes. J Exp Med. 1994 Mar 1;179(3):901–909. doi: 10.1084/jem.179.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bouvier M., Wiley D. C. Importance of peptide amino and carboxyl termini to the stability of MHC class I molecules. Science. 1994 Jul 15;265(5170):398–402. doi: 10.1126/science.8023162. [DOI] [PubMed] [Google Scholar]
  12. Campbell A. E., Foley F. L., Tevethia S. S. Demonstration of multiple antigenic sites of the SV40 transplantation rejection antigen by using cytotoxic T lymphocyte clones. J Immunol. 1983 Jan;130(1):490–492. [PubMed] [Google Scholar]
  13. Carreno B. M., Koenig S., Coligan J. E., Biddison W. E. The peptide binding specificity of HLA class I molecules is largely allele-specific and non-overlapping. Mol Immunol. 1992 Sep;29(9):1131–1140. doi: 10.1016/0161-5890(92)90046-z. [DOI] [PubMed] [Google Scholar]
  14. Carreno B. M., Turner R. V., Biddison W. E., Coligan J. E. Overlapping epitopes that are recognized by CD8+ HLA class I-restricted and CD4+ class II-restricted cytotoxic T lymphocytes are contained within an influenza nucleoprotein peptide. J Immunol. 1992 Feb 1;148(3):894–899. [PubMed] [Google Scholar]
  15. Casanova J. L., Martinon F., Gournier H., Barra C., Pannetier C., Regnault A., Kourilsky P., Cerottini J. C., Maryanski J. L. T cell receptor selection by and recognition of two class I major histocompatibility complex-restricted antigenic peptides that differ at a single position. J Exp Med. 1993 Mar 1;177(3):811–820. doi: 10.1084/jem.177.3.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cerundolo V., Alexander J., Anderson K., Lamb C., Cresswell P., McMichael A., Gotch F., Townsend A. Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature. 1990 May 31;345(6274):449–452. doi: 10.1038/345449a0. [DOI] [PubMed] [Google Scholar]
  17. Chen W., Khilko S., Fecondo J., Margulies D. H., McCluskey J. Determinant selection of major histocompatibility complex class I-restricted antigenic peptides is explained by class I-peptide affinity and is strongly influenced by nondominant anchor residues. J Exp Med. 1994 Oct 1;180(4):1471–1483. doi: 10.1084/jem.180.4.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Christinck E. R., Luscher M. A., Barber B. H., Williams D. B. Peptide binding to class I MHC on living cells and quantitation of complexes required for CTL lysis. Nature. 1991 Jul 4;352(6330):67–70. doi: 10.1038/352067a0. [DOI] [PubMed] [Google Scholar]
  19. Deckhut A. M., Lippolis J. D., Tevethia S. S. Comparative analysis of core amino acid residues of H-2D(b)-restricted cytotoxic T-lymphocyte recognition epitopes in simian virus 40 T antigen. J Virol. 1992 Jan;66(1):440–447. doi: 10.1128/jvi.66.1.440-447.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Deckhut A. M., Tevethia S. S. Effect of point mutations in the native simian virus 40 tumor antigen, and in synthetic peptides corresponding to the H-2Db-restricted epitopes, on antigen presentation and recognition by cytotoxic T lymphocyte clones. J Immunol. 1992 May 15;148(10):3012–3020. [PubMed] [Google Scholar]
  21. Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991 Sep 20;66(6):1145–1153. doi: 10.1016/0092-8674(91)90037-y. [DOI] [PubMed] [Google Scholar]
  22. Dick L. R., Aldrich C., Jameson S. C., Moomaw C. R., Pramanik B. C., Doyle C. K., DeMartino G. N., Bevan M. J., Forman J. M., Slaughter C. A. Proteolytic processing of ovalbumin and beta-galactosidase by the proteasome to a yield antigenic peptides. J Immunol. 1994 Apr 15;152(8):3884–3894. [PMC free article] [PubMed] [Google Scholar]
  23. Driscoll J., Brown M. G., Finley D., Monaco J. J. MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature. 1993 Sep 16;365(6443):262–264. doi: 10.1038/365262a0. [DOI] [PubMed] [Google Scholar]
  24. Eisenlohr L. C., Bacik I., Bennink J. R., Bernstein K., Yewdell J. W. Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes. Cell. 1992 Dec 11;71(6):963–972. doi: 10.1016/0092-8674(92)90392-p. [DOI] [PubMed] [Google Scholar]
  25. Eisenlohr L. C., Yewdell J. W., Bennink J. R. Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes. J Exp Med. 1992 Feb 1;175(2):481–487. doi: 10.1084/jem.175.2.481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Falk K., Rötzschke O., Stevanović S., Jung G., Rammensee H. G. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  28. Fehling H. J., Swat W., Laplace C., Kühn R., Rajewsky K., Müller U., von Boehmer H. MHC class I expression in mice lacking the proteasome subunit LMP-7. Science. 1994 Aug 26;265(5176):1234–1237. doi: 10.1126/science.8066463. [DOI] [PubMed] [Google Scholar]
  29. Fremont D. H., Matsumura M., Stura E. A., Peterson P. A., Wilson I. A. Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science. 1992 Aug 14;257(5072):919–927. doi: 10.1126/science.1323877. [DOI] [PubMed] [Google Scholar]
  30. Fu T. M., Bonneau R. H., Tevethia M. J., Tevethia S. S. Simian virus 40 T antigen as a carrier for the expression of cytotoxic T-lymphocyte recognition epitopes. J Virol. 1993 Nov;67(11):6866–6871. doi: 10.1128/jvi.67.11.6866-6871.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Gaczynska M., Rock K. L., Goldberg A. L. Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature. 1993 Sep 16;365(6443):264–267. doi: 10.1038/365264a0. [DOI] [PubMed] [Google Scholar]
  32. Gairin J. E., Oldstone M. B. Design of high-affinity major histocompatibility complex-specific antagonist peptides that inhibit cytotoxic T-lymphocyte activity: implications for control of viral disease. J Virol. 1992 Nov;66(11):6755–6762. doi: 10.1128/jvi.66.11.6755-6762.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Germain R. N., Margulies D. H. The biochemistry and cell biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi: 10.1146/annurev.iy.11.040193.002155. [DOI] [PubMed] [Google Scholar]
  34. Gould K., Cossins J., Bastin J., Brownlee G. G., Townsend A. A 15 amino acid fragment of influenza nucleoprotein synthesized in the cytoplasm is presented to class I-restricted cytotoxic T lymphocytes. J Exp Med. 1989 Sep 1;170(3):1051–1056. doi: 10.1084/jem.170.3.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  36. Hahn Y. S., Braciale V. L., Braciale T. J. Presentation of viral antigen to class I major histocompatibility complex-restricted cytotoxic T lymphocyte. Recognition of an immunodominant influenza hemagglutinin site by cytotoxic T lymphocyte is independent of the position of the site in the hemagglutinin translation product. J Exp Med. 1991 Sep 1;174(3):733–736. doi: 10.1084/jem.174.3.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Hahn Y. S., Hahn C. S., Braciale V. L., Braciale T. J., Rice C. M. CD8+ T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope. J Exp Med. 1992 Nov 1;176(5):1335–1341. doi: 10.1084/jem.176.5.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Hedrick S. M., Engel I., McElligott D. L., Fink P. J., Hsu M. L., Hansburg D., Matis L. A. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science. 1988 Mar 25;239(4847):1541–1544. doi: 10.1126/science.2832942. [DOI] [PubMed] [Google Scholar]
  39. Henderson R. A., Michel H., Sakaguchi K., Shabanowitz J., Appella E., Hunt D. F., Engelhard V. H. HLA-A2.1-associated peptides from a mutant cell line: a second pathway of antigen presentation. Science. 1992 Mar 6;255(5049):1264–1266. doi: 10.1126/science.1546329. [DOI] [PubMed] [Google Scholar]
  40. Jardetzky T. S., Lane W. S., Robinson R. A., Madden D. R., Wiley D. C. Identification of self peptides bound to purified HLA-B27. Nature. 1991 Sep 26;353(6342):326–329. doi: 10.1038/353326a0. [DOI] [PubMed] [Google Scholar]
  41. Joly E., Salvato M., Whitton J. L., Oldstone M. B. Polymorphism of cytotoxic T-lymphocyte clones that recognize a defined nine-amino-acid immunodominant domain of lymphocytic choriomeningitis virus glycoprotein. J Virol. 1989 May;63(5):1845–1851. doi: 10.1128/jvi.63.5.1845-1851.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kierstead T. D., Tevethia M. J. Association of p53 binding and immortalization of primary C57BL/6 mouse embryo fibroblasts by using simian virus 40 T-antigen mutants bearing internal overlapping deletion mutations. J Virol. 1993 Apr;67(4):1817–1829. doi: 10.1128/jvi.67.4.1817-1829.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
  44. Lai M. Z., Jang Y. J., Chen L. K., Gefter M. L. Restricted V-(D)-J junctional regions in the T cell response to lambda-repressor. Identification of residues critical for antigen recognition. J Immunol. 1990 Jun 15;144(12):4851–4856. [PubMed] [Google Scholar]
  45. Lill N. L., Tevethia M. J., Hendrickson W. G., Tevethia S. S. Cytotoxic T lymphocytes (CTL) against a transforming gene product select for transformed cells with point mutations within sequences encoding CTL recognition epitopes. J Exp Med. 1992 Aug 1;176(2):449–457. doi: 10.1084/jem.176.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Ljunggren H. G., Kärre K. Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism. J Exp Med. 1985 Dec 1;162(6):1745–1759. doi: 10.1084/jem.162.6.1745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
  48. Madden D. R., Garboczi D. N., Wiley D. C. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell. 1993 Nov 19;75(4):693–708. doi: 10.1016/0092-8674(93)90490-h. [DOI] [PubMed] [Google Scholar]
  49. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature. 1991 Sep 26;353(6342):321–325. doi: 10.1038/353321a0. [DOI] [PubMed] [Google Scholar]
  50. Milligan G. N., Morrison L. A., Gorka J., Braciale V. L., Braciale T. J. The recognition of a viral antigenic moiety by class I MHC-restricted cytolytic T lymphocytes is limited by the availability of the endogenously processed antigen. J Immunol. 1990 Nov 15;145(10):3188–3193. [PubMed] [Google Scholar]
  51. Momburg F., Roelse J., Howard J. C., Butcher G. W., Hämmerling G. J., Neefjes J. J. Selectivity of MHC-encoded peptide transporters from human, mouse and rat. Nature. 1994 Feb 17;367(6464):648–651. doi: 10.1038/367648a0. [DOI] [PubMed] [Google Scholar]
  52. Mylin L. M., Deckhut A. M., Bonneau R. H., Kierstead T. D., Tevethia M. J., Simmons D. T., Tevethi S. S. Cytotoxic T lymphocyte escape variants, induced mutations, and synthetic peptides define a dominant H-2Kb-restricted determinant in simian virus 40 tumor antigen. Virology. 1995 Apr 1;208(1):159–172. doi: 10.1006/viro.1995.1139. [DOI] [PubMed] [Google Scholar]
  53. Neefjes J. J., Momburg F., Hämmerling G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science. 1993 Aug 6;261(5122):769–771. doi: 10.1126/science.8342042. [DOI] [PubMed] [Google Scholar]
  54. Oldstone M. B., Whitton J. L., Lewicki H., Tishon A. Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes. J Exp Med. 1988 Aug 1;168(2):559–570. doi: 10.1084/jem.168.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Parker K. C., Bednarek M. A., Coligan J. E. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol. 1994 Jan 1;152(1):163–175. [PubMed] [Google Scholar]
  56. Potter T. A., Boyer C., Verhulst A. M., Golstein P., Rajan T. V. Expression of H-2Db on the cell surface in the absence of detectable beta 2 microglobulin. J Exp Med. 1984 Jul 1;160(1):317–322. doi: 10.1084/jem.160.1.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Rammensee H. G., Falk K., Rötzschke O. Peptides naturally presented by MHC class I molecules. Annu Rev Immunol. 1993;11:213–244. doi: 10.1146/annurev.iy.11.040193.001241. [DOI] [PubMed] [Google Scholar]
  58. Ruppert J., Sidney J., Celis E., Kubo R. T., Grey H. M., Sette A. Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell. 1993 Sep 10;74(5):929–937. doi: 10.1016/0092-8674(93)90472-3. [DOI] [PubMed] [Google Scholar]
  59. Rutila J. E., Imperiale M. J., Brockman W. W. Replication and transformation functions of in vitro-generated simian virus 40 large T antigen mutants. J Virol. 1986 May;58(2):526–535. doi: 10.1128/jvi.58.2.526-535.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Saito Y., Peterson P. A., Matsumura M. Quantitation of peptide anchor residue contributions to class I major histocompatibility complex molecule binding. J Biol Chem. 1993 Oct 5;268(28):21309–21317. [PubMed] [Google Scholar]
  61. Shibata K., Imarai M., van Bleek G. M., Joyce S., Nathenson S. G. Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3135–3139. doi: 10.1073/pnas.89.7.3135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Simmons D. T., Loeber G., Tegtmeyer P. Four major sequence elements of simian virus 40 large T antigen coordinate its specific and nonspecific DNA binding. J Virol. 1990 May;64(5):1973–1983. doi: 10.1128/jvi.64.5.1973-1983.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Stringer J. R. Mutant of simian virus 40 large T-antigen that is defective for viral DNA synthesis, but competent for transformation of cultured rat cells. J Virol. 1982 Jun;42(3):854–864. doi: 10.1128/jvi.42.3.854-864.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Stuber G., Modrow S., Höglund P., Franksson L., Elvin J., Wolf H., Kärre K., Klein G. Assessment of major histocompatibility complex class I interaction with Epstein-Barr virus and human immunodeficiency virus peptides by elevation of membrane H-2 and HLA in peptide loading-deficient cells. Eur J Immunol. 1992 Oct;22(10):2697–2703. doi: 10.1002/eji.1830221033. [DOI] [PubMed] [Google Scholar]
  65. Tanaka Y., Anderson R. W., Maloy W. L., Tevethia S. S. Localization of an immunorecessive epitope on SV40 T antigen by H-2Db-restricted cytotoxic T-lymphocyte clones and a synthetic peptide. Virology. 1989 Jul;171(1):205–213. doi: 10.1016/0042-6822(89)90527-8. [DOI] [PubMed] [Google Scholar]
  66. Tanaka Y., Tevethia M. J., Kalderon D., Smith A. E., Tevethia S. S. Clustering of antigenic sites recognized by cytotoxic T lymphocyte clones in the amino terminal half of SV40 T antigen. Virology. 1988 Feb;162(2):427–436. doi: 10.1016/0042-6822(88)90483-7. [DOI] [PubMed] [Google Scholar]
  67. Tanaka Y., Tevethia S. S. In vitro selection of SV40 T antigen epitope loss variants by site-specific cytotoxic T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4348–4354. [PubMed] [Google Scholar]
  68. Tanaka Y., Tevethia S. S. Loss of immunorecessive cytotoxic T lymphocyte determinant V on SV40 T antigen following cocultivation with site-specific cytotoxic T lymphocyte clone Y-5. Intervirology. 1990;31(2-4):197–202. doi: 10.1159/000150154. [DOI] [PubMed] [Google Scholar]
  69. Tevethia M. J. Immortalization of primary mouse embryo fibroblasts with SV40 virions, viral DNA, and a subgenomic DNA fragment in a quantitative assay. Virology. 1984 Sep;137(2):414–421. doi: 10.1016/0042-6822(84)90234-4. [DOI] [PubMed] [Google Scholar]
  70. Tevethia S. S., Lewis M., Tanaka Y., Milici J., Knowles B., Maloy W. L., Anderson R. Dissection of H-2Db-restricted cytotoxic T-lymphocyte epitopes on simian virus 40 T antigen by the use of synthetic peptides and H-2Dbm mutants. J Virol. 1990 Mar;64(3):1192–1200. doi: 10.1128/jvi.64.3.1192-1200.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Thompson D. L., Kalderon D., Smith A. E., Tevethia M. J. Dissociation of Rb-binding and anchorage-independent growth from immortalization and tumorigenicity using SV40 mutants producing N-terminally truncated large T antigens. Virology. 1990 Sep;178(1):15–34. doi: 10.1016/0042-6822(90)90375-2. [DOI] [PubMed] [Google Scholar]
  72. Townsend A., Bastin J., Gould K., Brownlee G., Andrew M., Coupar B., Boyle D., Chan S., Smith G. Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J Exp Med. 1988 Oct 1;168(4):1211–1224. doi: 10.1084/jem.168.4.1211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Townsend A., Elliott T., Cerundolo V., Foster L., Barber B., Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. doi: 10.1016/0092-8674(90)90366-m. [DOI] [PubMed] [Google Scholar]
  74. Townsend A., Ohlén C., Bastin J., Ljunggren H. G., Foster L., Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. doi: 10.1038/340443a0. [DOI] [PubMed] [Google Scholar]
  75. Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
  76. Van Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  77. Whitton J. L., Sheng N., Oldstone M. B., McKee T. A. A "string-of-beads" vaccine, comprising linked minigenes, confers protection from lethal-dose virus challenge. J Virol. 1993 Jan;67(1):348–352. doi: 10.1128/jvi.67.1.348-352.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Yanagi Y., Tishon A., Lewicki H., Cubitt B. A., Oldstone M. B. Diversity of T-cell receptors in virus-specific cytotoxic T lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule. J Virol. 1992 Apr;66(4):2527–2531. doi: 10.1128/jvi.66.4.2527-2531.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Yewdell J. W., Bennink J. R. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv Immunol. 1992;52:1–123. doi: 10.1016/s0065-2776(08)60875-5. [DOI] [PubMed] [Google Scholar]
  81. Young A. C., Zhang W., Sacchettini J. C., Nathenson S. G. The three-dimensional structure of H-2Db at 2.4 A resolution: implications for antigen-determinant selection. Cell. 1994 Jan 14;76(1):39–50. doi: 10.1016/0092-8674(94)90171-6. [DOI] [PubMed] [Google Scholar]
  82. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES