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. 1993 Dec 1;178(6):2173–2183. doi: 10.1084/jem.178.6.2173

Comparison of peptides bound to spleen and thymus class II

PMCID: PMC2191300  PMID: 8245790

Abstract

In the past we and others have suggested that positive selection of developing thymocytes may depend upon interaction between the alpha beta receptors on these cells and major histocompatibility complex (MHC) proteins bound to peptides found uniquely in the selecting tissue, thymus cortical epithelium. To test this hypothesis, peptides were isolated from MHC class II proteins of spleen, thymus cortical plus medullary epithelium, or thymus cortical epithelium alone. The results showed that the major peptides bound to class II on thymus cortical epithelium were also associated with spleen class II. Some peptides could only be detected in isolates from spleen, probably because of differences in the distribution or uptake of the donor proteins between spleen and thymus. Thus, although we found some tissue- specific distribution of self-peptides, our data suggest that there are no fundamental differences among these tissues in the occupancy of class II MHC by self-peptides. These results limit hypotheses which depend on a specialized mechanism of peptide generation and/or MHC class II loading to account for the positive selection of T cells on thymic cortical epithelium.

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Selected References

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  1. Ashton-Rickardt P. G., Van Kaer L., Schumacher T. N., Ploegh H. L., Tonegawa S. Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus. Cell. 1993 Jun 4;73(5):1041–1049. doi: 10.1016/0092-8674(93)90281-t. [DOI] [PubMed] [Google Scholar]
  2. Bevan M. J., Fink P. J. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978;42:3–19. doi: 10.1111/j.1600-065x.1978.tb00256.x. [DOI] [PubMed] [Google Scholar]
  3. Bix M., Raulet D. Inefficient positive selection of T cells directed by haematopoietic cells. Nature. 1992 Sep 24;359(6393):330–333. doi: 10.1038/359330a0. [DOI] [PubMed] [Google Scholar]
  4. Chiang H. L., Terlecky S. R., Plant C. P., Dice J. F. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science. 1989 Oct 20;246(4928):382–385. doi: 10.1126/science.2799391. [DOI] [PubMed] [Google Scholar]
  5. De Magistris M. T., Alexander J., Coggeshall M., Altman A., Gaeta F. C., Grey H. M., Sette A. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor. Cell. 1992 Feb 21;68(4):625–634. doi: 10.1016/0092-8674(92)90139-4. [DOI] [PubMed] [Google Scholar]
  6. Delespesse G., Sarfati M., Hofstetter H., Suter U., Nakajima T., Peleman R., Letellier M., Kilchherr E., Frost H. Structure, function and clinical relevance of the low affinity receptor for IgE. Immunol Invest. 1988 Jul;17(5):363–387. doi: 10.3109/08820138809049845. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Farr A. G., Nakane P. K. Cells bearing Ia antigens in the murine thymus. An ultrastructural study. Am J Pathol. 1983 Apr;111(1):88–97. [PMC free article] [PubMed] [Google Scholar]
  9. Finkel T. H., Cambier J. C., Kubo R. T., Born W. K., Marrack P., Kappler J. W. The thymus has two functionally distinct populations of immature alpha beta + T cells: one population is deleted by ligation of alpha beta TCR. Cell. 1989 Sep 22;58(6):1047–1054. doi: 10.1016/0092-8674(89)90503-5. [DOI] [PubMed] [Google Scholar]
  10. Fung-Leung W. P., Schilham M. W., Rahemtulla A., Kündig T. M., Vollenweider M., Potter J., van Ewijk W., Mak T. W. CD8 is needed for development of cytotoxic T cells but not helper T cells. Cell. 1991 May 3;65(3):443–449. doi: 10.1016/0092-8674(91)90462-8. [DOI] [PubMed] [Google Scholar]
  11. Guillet J. G., Lai M. Z., Briner T. J., Smith J. A., Gefter M. L. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature. 1986 Nov 20;324(6094):260–262. doi: 10.1038/324260a0. [DOI] [PubMed] [Google Scholar]
  12. Hedrick S. M., Matis L. A., Hecht T. T., Samelson L. E., Longo D. L., Heber-Katz E., Schwartz R. H. The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c. Cell. 1982 Aug;30(1):141–152. doi: 10.1016/0092-8674(82)90020-4. [DOI] [PubMed] [Google Scholar]
  13. Hunt D. F., Michel H., Dickinson T. A., Shabanowitz J., Cox A. L., Sakaguchi K., Appella E., Grey H. M., Sette A. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science. 1992 Jun 26;256(5065):1817–1820. doi: 10.1126/science.1319610. [DOI] [PubMed] [Google Scholar]
  14. Jameson S. C., Carbone F. R., Bevan M. J. Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells. J Exp Med. 1993 Jun 1;177(6):1541–1550. doi: 10.1084/jem.177.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Kappler J., White J., Wegmann D., Mustain E., Marrack P. Antigen presentation by Ia+ B cell hybridomas to H-2-restricted T cell hybridomas. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3604–3607. doi: 10.1073/pnas.79.11.3604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Koller B. H., Marrack P., Kappler J. W., Smithies O. Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science. 1990 Jun 8;248(4960):1227–1230. doi: 10.1126/science.2112266. [DOI] [PubMed] [Google Scholar]
  20. Kourilsky P., Claverie J. M. MHC restriction, alloreactivity, and thymic education: a common link? Cell. 1989 Feb 10;56(3):327–329. doi: 10.1016/0092-8674(89)90233-x. [DOI] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Leighton J., Sette A., Sidney J., Appella E., Ehrhardt C., Fuchs S., Adorini L. Comparison of structural requirements for interaction of the same peptide with I-Ek and I-Ed molecules in the activation of MHC class II-restricted T cells. J Immunol. 1991 Jul 1;147(1):198–204. [PubMed] [Google Scholar]
  23. Marrack P., Kappler J. The T cell receptor. Science. 1987 Nov 20;238(4830):1073–1079. doi: 10.1126/science.3317824. [DOI] [PubMed] [Google Scholar]
  24. Marrack P., McCormack J., Kappler J. Presentation of antigen, foreign major histocompatibility complex proteins and self by thymus cortical epithelium. Nature. 1989 Apr 6;338(6215):503–505. doi: 10.1038/338503a0. [DOI] [PubMed] [Google Scholar]
  25. Metzger H. Transmembrane signaling: the joy of aggregation. J Immunol. 1992 Sep 1;149(5):1477–1487. [PubMed] [Google Scholar]
  26. Murphy D. B., Lo D., Rath S., Brinster R. L., Flavell R. A., Slanetz A., Janeway C. A., Jr A novel MHC class II epitope expressed in thymic medulla but not cortex. Nature. 1989 Apr 27;338(6218):765–768. doi: 10.1038/338765a0. [DOI] [PubMed] [Google Scholar]
  27. Murphy K. M., Heimberger A. B., Loh D. Y. Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. Science. 1990 Dec 21;250(4988):1720–1723. doi: 10.1126/science.2125367. [DOI] [PubMed] [Google Scholar]
  28. Pawlowski T., Elliott J. D., Loh D. Y., Staerz U. D. Positive selection of T lymphocytes on fibroblasts. Nature. 1993 Aug 12;364(6438):642–645. doi: 10.1038/364642a0. [DOI] [PubMed] [Google Scholar]
  29. Racioppi L., Ronchese F., Matis L. A., Germain R. N. Peptide-major histocompatibility complex class II complexes with mixed agonist/antagonist properties provide evidence for ligand-related differences in T cell receptor-dependent intracellular signaling. J Exp Med. 1993 Apr 1;177(4):1047–1060. doi: 10.1084/jem.177.4.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ramsdell F., Fowlkes B. J. Engagement of CD4 and CD8 accessory molecules is required for T cell maturation. J Immunol. 1989 Sep 1;143(5):1467–1471. [PubMed] [Google Scholar]
  31. Robey E. A., Ramsdell F., Kioussis D., Sha W., Loh D., Axel R., Fowlkes B. J. The level of CD8 expression can determine the outcome of thymic selection. Cell. 1992 Jun 26;69(7):1089–1096. doi: 10.1016/0092-8674(92)90631-l. [DOI] [PubMed] [Google Scholar]
  32. Rosloniec E. F., Gay D., Freed J. H. Epitopic analysis by anti-I-Ak monoclonal antibodies of I-Ak-restricted presentation of lysozyme peptides. J Immunol. 1989 Jun 15;142(12):4176–4183. [PubMed] [Google Scholar]
  33. Rosloniec E. F., Vitez L. J., Buus S., Freed J. H. MHC class II-derived peptides can bind to class II molecules, including self molecules, and prevent antigen presentation. J Exp Med. 1990 May 1;171(5):1419–1430. doi: 10.1084/jem.171.5.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rudensky AYu, Preston-Hurlburt P., Hong S. C., Barlow A., Janeway C. A., Jr Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991 Oct 17;353(6345):622–627. doi: 10.1038/353622a0. [DOI] [PubMed] [Google Scholar]
  35. Sadegh-Nasseri S., Germain R. N. A role for peptide in determining MHC class II structure. Nature. 1991 Sep 12;353(6340):167–170. doi: 10.1038/353167a0. [DOI] [PubMed] [Google Scholar]
  36. Sakaguchi N., Kashiwamura S., Kimoto M., Thalmann P., Melchers F. B lymphocyte lineage-restricted expression of mb-1, a gene with CD3-like structural properties. EMBO J. 1988 Nov;7(11):3457–3464. doi: 10.1002/j.1460-2075.1988.tb03220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sha W. C., Nelson C. A., Newberry R. D., Pullen J. K., Pease L. R., Russell J. H., Loh D. Y. Positive selection of transgenic receptor-bearing thymocytes by Kb antigen is altered by Kb mutations that involve peptide binding. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6186–6190. doi: 10.1073/pnas.87.16.6186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shastri N., Gammon G., Miller A., Sercarz E. E. Ia molecule-associated selectivity in T cell recognition of a 23-amino-acid peptide of lysozyme. J Exp Med. 1986 Sep 1;164(3):882–896. doi: 10.1084/jem.164.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sherman L. A., Hesse S. V., Irwin M. J., La Face D., Peterson P. Selecting T cell receptors with high affinity for self-MHC by decreasing the contribution of CD8. Science. 1992 Oct 30;258(5083):815–818. doi: 10.1126/science.1439792. [DOI] [PubMed] [Google Scholar]
  40. Sloan-Lancaster J., Evavold B. D., Allen P. M. Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature. 1993 May 13;363(6425):156–159. doi: 10.1038/363156a0. [DOI] [PubMed] [Google Scholar]
  41. Sprent J., Lo D., Gao E. K., Ron Y. T cell selection in the thymus. Immunol Rev. 1988 Jan;101:173–190. doi: 10.1111/j.1600-065x.1988.tb00737.x. [DOI] [PubMed] [Google Scholar]
  42. Stern L. J., Wiley D. C. The human class II MHC protein HLA-DR1 assembles as empty alpha beta heterodimers in the absence of antigenic peptide. Cell. 1992 Feb 7;68(3):465–477. doi: 10.1016/0092-8674(92)90184-e. [DOI] [PubMed] [Google Scholar]
  43. Symer D. E., Dintzis R. Z., Diamond D. J., Dintzis H. M. Inhibition or activation of human T cell receptor transfectants is controlled by defined, soluble antigen arrays. J Exp Med. 1992 Nov 1;176(5):1421–1430. doi: 10.1084/jem.176.5.1421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Weiss A. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. Cell. 1993 Apr 23;73(2):209–212. doi: 10.1016/0092-8674(93)90221-b. [DOI] [PubMed] [Google Scholar]
  45. White J., Haskins K. M., Marrack P., Kappler J. Use of I region-restricted, antigen-specific T cell hybridomas to produce idiotypically specific anti-receptor antibodies. J Immunol. 1983 Mar;130(3):1033–1037. [PubMed] [Google Scholar]
  46. White J., Pullen A., Choi K., Marrack P., Kappler J. W. Antigen recognition properties of mutant V beta 3+ T cell receptors are consistent with an immunoglobulin-like structure for the receptor. J Exp Med. 1993 Jan 1;177(1):119–125. doi: 10.1084/jem.177.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. van Ewijk W., Ron Y., Monaco J., Kappler J., Marrack P., Le Meur M., Gerlinger P., Durand B., Benoist C., Mathis D. Compartmentalization of MHC class II gene expression in transgenic mice. Cell. 1988 May 6;53(3):357–370. doi: 10.1016/0092-8674(88)90156-0. [DOI] [PubMed] [Google Scholar]

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