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. 1989 Jul;8(7):1947–1952. doi: 10.1002/j.1460-2075.1989.tb03599.x

Minimum length of an idiotypic peptide and a model for its binding to a major histocompatibility complex class II molecule.

B Bogen 1, J D Lambris 1
PMCID: PMC401055  PMID: 2792076

Abstract

We have defined the minimum length of a synthetic peptide which can activate I-Ed-restricted BALB/c T cell clones specific for a mutated self-antigen: an idiotope on the syngeneic lambda 2315 immunoglobulin light chain. A peptide comprising residues 91-101 of the lambda 2315 sequence had full stimulatory potency. Surprisingly, a peptide analogue in which His97 was deleted was almost fully active. Truncated, deleted or substituted peptide analogues did not distinguish between seven T cell clones that use different alpha/beta T cell receptors. The 91-101 region in the lambda 2315 light chain does not form an amphipathic helix even though such a helix has been suggested to be important for T cell epitopes. Further, a motif proposed by Rothbard and Taylor as being common to T cell immunogenic peptides is not necessary for the lambda 2315 idiotypic peptide. Comparison with seven other I-Ed-restricted peptides revealed that the peptides are generally positively charged and have two basic amino acids clustered around the centre. On the basis of a model of the class II molecule peptide binding site, we suggest that these positively charged residues may interact with the negatively charged residues at positions 114(Glu) and 155(Asp) of the E beta d chain.

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Selected References

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  1. Adorini L., Sette A., Buus S., Grey H. M., Darsley M., Lehmann P. V., Doria G., Nagy Z. A., Appella E. Interaction of an immunodominant epitope with Ia molecules in T-cell activation. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5181–5185. doi: 10.1073/pnas.85.14.5181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  4. Berkower I., Buckenmeyer G. K., Berzofsky J. A. Molecular mapping of a histocompatibility-restricted immunodominant T cell epitope with synthetic and natural peptides: implications for T cell antigenic structure. J Immunol. 1986 Apr 1;136(7):2498–2503. [PubMed] [Google Scholar]
  5. Berkower I., Kawamura H., Matis L. A., Berzofsky J. A. T cell clones to two major T cell epitopes of myoglobin: effect of I-A/I-E restriction on epitope dominance. J Immunol. 1985 Oct;135(4):2628–2634. [PubMed] [Google Scholar]
  6. Blomberg B., Tonegawa S. DNA sequences of the joining regions of mouse lambda light chain immunoglobulin genes. Proc Natl Acad Sci U S A. 1982 Jan;79(2):530–533. doi: 10.1073/pnas.79.2.530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bogen B., Jørgensen T., Hannestad K. T helper cell recognition of idiotopes on lambda 2 light chains of M315 and T952: evidence for dependence on somatic mutations in the third hypervariable region. Eur J Immunol. 1985 Mar;15(3):278–281. doi: 10.1002/eji.1830150313. [DOI] [PubMed] [Google Scholar]
  8. Bogen B., Malissen B., Haas W. Idiotope-specific T cell clones that recognize syngeneic immunoglobulin fragments in the context of class II molecules. Eur J Immunol. 1986 Nov;16(11):1373–1378. doi: 10.1002/eji.1830161110. [DOI] [PubMed] [Google Scholar]
  9. Bogen B., Snodgrass R., Briand J. P., Hannestad K. Synthetic peptides and beta-chain gene rearrangements reveal a diversified T cell repertoire for a lambda light chain third hypervariable region. Eur J Immunol. 1986 Nov;16(11):1379–1384. doi: 10.1002/eji.1830161111. [DOI] [PubMed] [Google Scholar]
  10. Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Somatic variants of murine immunoglobulin lambda light chains. Nature. 1982 Jul 22;298(5872):380–382. doi: 10.1038/298380a0. [DOI] [PubMed] [Google Scholar]
  11. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  12. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  13. Claverie J. M., Kourilsky P., Langlade-Demoyen P., Chalufour-Prochnicka A., Dadaglio G., Tekaia F., Plata F., Bougueleret L. T-immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein. Eur J Immunol. 1988 Oct;18(10):1547–1553. doi: 10.1002/eji.1830181012. [DOI] [PubMed] [Google Scholar]
  14. Dembić Z., Haas W., Weiss S., McCubrey J., Kiefer H., von Boehmer H., Steinmetz M. Transfer of specificity by murine alpha and beta T-cell receptor genes. Nature. 1986 Mar 20;320(6059):232–238. doi: 10.1038/320232a0. [DOI] [PubMed] [Google Scholar]
  15. Finnegan A., Smith M. A., Smith J. A., Berzofsky J., Sachs D. H., Hodes R. J. The T cell repertoire for recognition of a phylogenetically distant protein antigen. Peptide specificity and MHC restriction of staphylococcal nuclease-specific T cell clones. J Exp Med. 1986 Sep 1;164(3):897–910. doi: 10.1084/jem.164.3.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  17. Hackett C. J., 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.158.2.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hannestad K., Kristoffersen G., Briand J. P. The T lymphocyte response to syngeneic lambda 2 light chain idiotopes. Significance of individual amino acids revealed by variant lambda 2 chains and idiotope-mimicking chemically synthesized peptides. Eur J Immunol. 1986 Aug;16(8):889–893. doi: 10.1002/eji.1830160803. [DOI] [PubMed] [Google Scholar]
  19. Heber-Katz E., Hollosi M., Dietzschold B., Hudecz F., Fasman G. D. The T cell response to the glycoprotein D of the herpes simplex virus: the significance of antigen conformation. J Immunol. 1985 Aug;135(2):1385–1390. [PubMed] [Google Scholar]
  20. Hyldig-Nielsen J. J., Schenning L., Hammerling U., Widmark E., Heldin E., Lind P., Servenius B., Lund T., Flavell R., Lee J. S. The complete nucleotide sequence of the I-E alpha d immune response gene. Nucleic Acids Res. 1983 Aug 11;11(15):5055–5071. doi: 10.1093/nar/11.15.5055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Janeway C. A., Jr, Sakato N., Eisen H. N. Recognition of immunoglobulin idiotypes by thymus-derived lymphocytes. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2357–2360. doi: 10.1073/pnas.72.6.2357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Livingstone A. M., Fathman C. G. The structure of T-cell epitopes. Annu Rev Immunol. 1987;5:477–501. doi: 10.1146/annurev.iy.05.040187.002401. [DOI] [PubMed] [Google Scholar]
  23. Lorenz R. G., Allen P. M. Direct evidence for functional self-protein/Ia-molecule complexes in vivo. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5220–5223. doi: 10.1073/pnas.85.14.5220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lynch R. G., Graff R. J., Sirisinha S., Simms E. S., Eisen H. N. Myeloma proteins as tumor-specific transplantation antigens. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1540–1544. doi: 10.1073/pnas.69.6.1540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Malissen B., Price M. P., Goverman J. M., McMillan M., White J., Kappler J., Marrack P., Pierres A., Pierres M., Hood L. Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines. Cell. 1984 Feb;36(2):319–327. doi: 10.1016/0092-8674(84)90225-3. [DOI] [PubMed] [Google Scholar]
  26. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  27. Miller J., Selsing E., Storb U. Structural alterations in J regions of mouse immunoglobulin lambda genes are associated with differential gene expression. Nature. 1982 Feb 4;295(5848):428–430. doi: 10.1038/295428a0. [DOI] [PubMed] [Google Scholar]
  28. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sette A., Buus S., Colon S., Smith J. A., Miles C., Grey H. M. Structural characteristics of an antigen required for its interaction with Ia and recognition by T cells. 1987 Jul 30-Aug 5Nature. 328(6129):395–399. doi: 10.1038/328395a0. [DOI] [PubMed] [Google Scholar]
  30. Sirisinha S., Eisen H. N. Autoimmune-like antibodies to the ligand-binding sites of myeloma proteins. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3130–3135. doi: 10.1073/pnas.68.12.3130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tonegawa S., Maxam A. M., Tizard R., Bernard O., Gilbert W. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1485–1489. doi: 10.1073/pnas.75.3.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Weiss S., Bogen B. B-lymphoma cells process and present their endogenous immunoglobulin to major histocompatibility complex-restricted T cells. Proc Natl Acad Sci U S A. 1989 Jan;86(1):282–286. doi: 10.1073/pnas.86.1.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wekerle H., Schwab M., Linington C., Meyermann R. Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes. Eur J Immunol. 1986 Dec;16(12):1551–1557. doi: 10.1002/eji.1830161214. [DOI] [PubMed] [Google Scholar]
  34. Winchester G., Sunshine G. H., Nardi N., Mitchison N. A. Antigen-presenting cells do not discriminate between self and nonself. Immunogenetics. 1984;19(6):487–491. doi: 10.1007/BF00403439. [DOI] [PubMed] [Google Scholar]

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