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. 1995 Feb 1;181(2):787–792. doi: 10.1084/jem.181.2.787

Increase in positive selection of CD8+ T cells in TAP1-mutant mice by human beta 2-microglobulin transgene

PMCID: PMC2191882  PMID: 7836931

Abstract

Mice harboring a deletion of the gene encoding the transporter associated with antigen presentation-1 (TAP1) are impaired in providing major histocompatibility complex (MHC) class I molecules with peptides of cytosolic origin and lack stable MHC class I cell surface expression. They consequently have a strongly reduced number of CD8+ T cells. To examine whether selection of CD8+ T cells is dependent on TAP- dependent peptides, we partially restored MHC class I cell surface expression in TAP1-deficient mice by introduction of human beta 2- microglobulin. We show that selection of functional CD8+ T cells can be augmented in vivo in the absence of TAP1-dependent peptides.

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Selected References

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  1. Aldrich C. J., Ljunggren H. G., Van Kaer L., Ashton-Rickardt P. G., Tonegawa S., Forman J. Positive selection of self- and alloreactive CD8+ T cells in Tap-1 mutant mice. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6525–6528. doi: 10.1073/pnas.91.14.6525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander J., Payne J. A., Murray R., Frelinger J. A., Cresswell P. Differential transport requirements of HLA and H-2 class I glycoproteins. Immunogenetics. 1989;29(6):380–388. doi: 10.1007/BF00375866. [DOI] [PubMed] [Google Scholar]
  3. Anderson K. S., Alexander J., Wei M., Cresswell P. Intracellular transport of class I MHC molecules in antigen processing mutant cell lines. J Immunol. 1993 Oct 1;151(7):3407–3419. [PubMed] [Google Scholar]
  4. Apasov S., Sitkovsky M. Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2-microglobulin, MHC class I-deficient mice. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2837–2841. doi: 10.1073/pnas.90.7.2837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ashton-Rickardt P. G., Bandeira A., Delaney J. R., Van Kaer L., Pircher H. P., Zinkernagel R. M., Tonegawa S. Evidence for a differential avidity model of T cell selection in the thymus. Cell. 1994 Feb 25;76(4):651–663. doi: 10.1016/0092-8674(94)90505-3. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Glas R., Ohlén C., Höglund P., Kärre K. The CD8+ T cell repertoire in beta 2-microglobulin-deficient mice is biased towards reactivity against self-major histocompatibility class I. J Exp Med. 1994 Feb 1;179(2):661–672. doi: 10.1084/jem.179.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Heemels M. T., Ploegh H. Antigen presentation: untapped peptides. Curr Biol. 1993 Jun 1;3(6):380–383. doi: 10.1016/0960-9822(93)90208-6. [DOI] [PubMed] [Google Scholar]
  10. Hogquist K. A., Gavin M. A., Bevan M. J. Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture. J Exp Med. 1993 May 1;177(5):1469–1473. doi: 10.1084/jem.177.5.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hogquist K. A., Jameson S. C., Heath W. R., Howard J. L., Bevan M. J., Carbone F. R. T cell receptor antagonist peptides induce positive selection. Cell. 1994 Jan 14;76(1):17–27. doi: 10.1016/0092-8674(94)90169-4. [DOI] [PubMed] [Google Scholar]
  12. Kast W. M., Roux L., Curren J., Blom H. J., Voordouw A. C., Meloen R. H., Kolakofsky D., Melief C. J. Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2283–2287. doi: 10.1073/pnas.88.6.2283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lamousé-Smith E., Clements V. K., Ostrand-Rosenberg S. Beta 2M-/- knockout mice contain low levels of CD8+ cytotoxic T lymphocyte that mediate specific tumor rejection. J Immunol. 1993 Dec 1;151(11):6283–6290. [PubMed] [Google Scholar]
  14. 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]
  15. Neefjes J. J., Breur-Vriesendorp B. S., van Seventer G. A., Iványi P., Ploegh H. L. An improved biochemical method for the analysis of HLA-class I antigens. Definition of new HLA-class I subtypes. Hum Immunol. 1986 Jun;16(2):169–181. doi: 10.1016/0198-8859(86)90046-7. [DOI] [PubMed] [Google Scholar]
  16. Neefjes J. J., Dierx J., Ploegh H. L. The effect of anchor residue modifications on the stability of major histocompatibility complex class I-peptide interactions. Eur J Immunol. 1993 Apr;23(4):840–845. doi: 10.1002/eji.1830230411. [DOI] [PubMed] [Google Scholar]
  17. Schumacher T. N., De Bruijn M. L., Vernie L. N., Kast W. M., Melief C. J., Neefjes J. J., Ploegh H. L. Peptide selection by MHC class I molecules. Nature. 1991 Apr 25;350(6320):703–706. doi: 10.1038/350703a0. [DOI] [PubMed] [Google Scholar]
  18. Schumacher T. N., Heemels M. T., Neefjes J. J., Kast W. M., Melief C. J., Ploegh H. L. Direct binding of peptide to empty MHC class I molecules on intact cells and in vitro. Cell. 1990 Aug 10;62(3):563–567. doi: 10.1016/0092-8674(90)90020-f. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Van Kaer L., Ashton-Rickardt P. G., Ploegh H. L., Tonegawa S. TAP1 mutant mice are deficient in antigen presentation, surface class I molecules, and CD4-8+ T cells. Cell. 1992 Dec 24;71(7):1205–1214. doi: 10.1016/s0092-8674(05)80068-6. [DOI] [PubMed] [Google Scholar]
  21. Wei M. L., Cresswell P. HLA-A2 molecules in an antigen-processing mutant cell contain signal sequence-derived peptides. Nature. 1992 Apr 2;356(6368):443–446. doi: 10.1038/356443a0. [DOI] [PubMed] [Google Scholar]
  22. von Boehmer H. Positive selection of lymphocytes. Cell. 1994 Jan 28;76(2):219–228. doi: 10.1016/0092-8674(94)90330-1. [DOI] [PubMed] [Google Scholar]

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