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. 1993 Oct 1;178(4):1453–1458. doi: 10.1084/jem.178.4.1453

Epitope-specific enhancement of antigen presentation by invariant chain

PMCID: PMC2191208  PMID: 7690835

Abstract

The MHC class II-associated invariant chain (Ii) is involved in the intracellular sorting of class II molecules to the endocytic pathway where peptides from processed exogenous antigens are bound, and thereby Ii is thought to enhance antigen presentation. Here we demonstrate that presentation of only one out of five epitopes of a given antigen is augmented by Ii. We have compared the presentation of five different epitopes derived from hen egg white lysozyme (HEL) to Ak-restricted T hybridomas by rat-2 fibroblasts transfected with A alpha k and A beta k (RKK) and RKK cells supertransfected with the mouse invariant chain (RKKI). Only the presentation of the HEL epitope 46-61 was enhanced whereas the presentation of the HEL epitopes 25-43, 34-45, 112-124, and 116-129 was unchanged or even slightly diminished in RKKI cells. The presentation of the epitopes 25-43 and 34-45 was virtually insensitive to the lysosomotropic reagent chloroquine. Brefeldin A (BFA), which inhibits protein egress from the endoplasmic reticulum, blocked the presentation of all epitopes tested in RKKI cells. In contrast, in Ii- negative RKK cells only the presentation of the epitope HEL(46-61) was inhibited by BFA and the presentation of the epitopes 25-43 and 34-45 was only slightly impaired. These findings suggest that Ii may target class II molecules to selected endosomal subcompartments involved in the processing of different peptides derived from an endocytosed antigen. As a result, the enhancement of the class II-restricted presentation in Ii expressing cells appears to be epitope specific rather than antigen specific.

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Selected References

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  1. Adorini L., Appella E., Doria G., Nagy Z. A. Mechanisms influencing the immunodominance of T cell determinants. J Exp Med. 1988 Dec 1;168(6):2091–2104. doi: 10.1084/jem.168.6.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adorini L., Moreno J., Momburg F., Hämmerling G. J., Guéry J. C., Valli A., Fuchs S. Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells. J Exp Med. 1991 Oct 1;174(4):945–948. doi: 10.1084/jem.174.4.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allen P. M., Unanue E. R. Differential requirements for antigen processing by macrophages for lysozyme-specific T cell hybridomas. J Immunol. 1984 Mar;132(3):1077–1079. [PubMed] [Google Scholar]
  4. Anderson M. S., Miller J. Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2282–2286. doi: 10.1073/pnas.89.6.2282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bakke O., Dobberstein B. MHC class II-associated invariant chain contains a sorting signal for endosomal compartments. Cell. 1990 Nov 16;63(4):707–716. doi: 10.1016/0092-8674(90)90137-4. [DOI] [PubMed] [Google Scholar]
  6. Bertolino P., Forquet F., Pont S., Koch N., Gerlier D., Rabourdin-Combe C. Correlation between invariant chain expression level and capability to present antigen to MHC class II-restricted T cells. Int Immunol. 1991 May;3(5):435–443. doi: 10.1093/intimm/3.5.435. [DOI] [PubMed] [Google Scholar]
  7. Collins D. S., Unanue E. R., Harding C. V. Reduction of disulfide bonds within lysosomes is a key step in antigen processing. J Immunol. 1991 Dec 15;147(12):4054–4059. [PubMed] [Google Scholar]
  8. Guéry J. C., Sette A., Leighton J., Dragomir A., Adorini L. Selective immunosuppression by administration of major histocompatibility complex (MHC) class II-binding peptides. I. Evidence for in vivo MHC blockade preventing T cell activation. J Exp Med. 1992 May 1;175(5):1345–1352. doi: 10.1084/jem.175.5.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harding C. V., Collins D. S., Slot J. W., Geuze H. J., Unanue E. R. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Cell. 1991 Jan 25;64(2):393–401. doi: 10.1016/0092-8674(91)90647-h. [DOI] [PubMed] [Google Scholar]
  10. Harding C. V., Roof R. W., Allen P. M., Unanue E. R. Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2740–2744. doi: 10.1073/pnas.88.7.2740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lamb C. A., Yewdell J. W., Bennink J. R., Cresswell P. Invariant chain targets HLA class II molecules to acidic endosomes containing internalized influenza virus. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):5998–6002. doi: 10.1073/pnas.88.14.5998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Layet C., Germain R. N. Invariant chain promotes egress of poorly expressed, haplotype-mismatched class II major histocompatibility complex A alpha A beta dimers from the endoplasmic reticulum/cis-Golgi compartment. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2346–2350. doi: 10.1073/pnas.88.6.2346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lippincott-Schwartz J., Yuan L., Tipper C., Amherdt M., Orci L., Klausner R. D. Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic. Cell. 1991 Nov 1;67(3):601–616. doi: 10.1016/0092-8674(91)90534-6. [DOI] [PubMed] [Google Scholar]
  14. Lorenz R. G., Tyler A. N., Allen P. M. T cell recognition of bovine ribonuclease. Self/non-self discrimination at the level of binding to the I-Ak molecule. J Immunol. 1988 Dec 15;141(12):4124–4128. [PubMed] [Google Scholar]
  15. Lotteau V., Teyton L., Peleraux A., Nilsson T., Karlsson L., Schmid S. L., Quaranta V., Peterson P. A. Intracellular transport of class II MHC molecules directed by invariant chain. Nature. 1990 Dec 13;348(6302):600–605. doi: 10.1038/348600a0. [DOI] [PubMed] [Google Scholar]
  16. Nadimi F., Moreno J., Momburg F., Heuser A., Fuchs S., Adorini L., Hämmerling G. J. Antigen presentation of hen egg-white lysozyme but not of ribonuclease A is augmented by the major histocompatibility complex class II-associated invariant chain. Eur J Immunol. 1991 May;21(5):1255–1263. doi: 10.1002/eji.1830210524. [DOI] [PubMed] [Google Scholar]
  17. Nowell J., Quaranta V. Chloroquine affects biosynthesis of Ia molecules by inhibiting dissociation of invariant (gamma) chains from alpha-beta dimers in B cells. J Exp Med. 1985 Oct 1;162(4):1371–1376. doi: 10.1084/jem.162.4.1371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peters P. J., Neefjes J. J., Oorschot V., Ploegh H. L., Geuze H. J. Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature. 1991 Feb 21;349(6311):669–676. doi: 10.1038/349669a0. [DOI] [PubMed] [Google Scholar]
  19. Peterson M., Miller J. Antigen presentation enhanced by the alternatively spliced invariant chain gene product p41. Nature. 1992 Jun 18;357(6379):596–598. doi: 10.1038/357596a0. [DOI] [PubMed] [Google Scholar]
  20. Peterson M., Miller J. Invariant chain influences the immunological recognition of MHC class II molecules. Nature. 1990 May 10;345(6271):172–174. doi: 10.1038/345172a0. [DOI] [PubMed] [Google Scholar]
  21. Roche P. A., Cresswell P. Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. Nature. 1990 Jun 14;345(6276):615–618. doi: 10.1038/345615a0. [DOI] [PubMed] [Google Scholar]
  22. Sette A., Southwood S., O'Sullivan D., Gaeta F. C., Sidney J., Grey H. M. Effect of pH on MHC class II-peptide interactions. J Immunol. 1992 Feb 1;148(3):844–851. [PubMed] [Google Scholar]
  23. St-Pierre Y., Watts T. H. MHC class II-restricted presentation of native protein antigen by B cells is inhibitable by cycloheximide and brefeldin A. J Immunol. 1990 Aug 1;145(3):812–818. [PubMed] [Google Scholar]
  24. Stockinger B., Pessara U., Lin R. H., Habicht J., Grez M., Koch N. A role of Ia-associated invariant chains in antigen processing and presentation. Cell. 1989 Feb 24;56(4):683–689. doi: 10.1016/0092-8674(89)90590-4. [DOI] [PubMed] [Google Scholar]
  25. Viville S., Neefjes J., Lotteau V., Dierich A., Lemeur M., Ploegh H., Benoist C., Mathis D. Mice lacking the MHC class II-associated invariant chain. Cell. 1993 Feb 26;72(4):635–648. doi: 10.1016/0092-8674(93)90081-z. [DOI] [PubMed] [Google Scholar]
  26. Wood S. A., Brown W. J. The morphology but not the function of endosomes and lysosomes is altered by brefeldin A. J Cell Biol. 1992 Oct;119(2):273–285. doi: 10.1083/jcb.119.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]

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