Abstract
Mice with a homozygous deletion in their Tap-1 gene (-/- mice) express very low levels of cell membrane major histocompatibility complex class I molecules and have < 1% peripheral CD8+ T cells. We show that these -/- mice but not their +/- littermates display strong primary syngeneic anti-H-2Kb and -Db-specific responses mediated by CD8+ T cells. These responses are augmented by in vivo priming. Further, -/- mice primed in vivo with H-2d alloantigens generate an anti-H-2d response which appears nearly as strong as that found in +/- littermates. Both -/- anti-H-2b and anti-H-2d T cells do not recognize target cells from Tap-1 -/- animals or Tap-2-deficient RMA-S cells. Thus, some CD8+ anti-self and alloreactive T cells can be selected in the absence of Tap proteins.
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- 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]
- 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]
- 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]
- Attaya M., Jameson S., Martinez C. K., Hermel E., Aldrich C., Forman J., Lindahl K. F., Bevan M. J., Monaco J. J. Ham-2 corrects the class I antigen-processing defect in RMA-S cells. Nature. 1992 Feb 13;355(6361):647–649. doi: 10.1038/355647a0. [DOI] [PubMed] [Google Scholar]
- Berg L. J., Frank G. D., Davis M. M. The effects of MHC gene dosage and allelic variation on T cell receptor selection. Cell. 1990 Mar 23;60(6):1043–1053. doi: 10.1016/0092-8674(90)90352-f. [DOI] [PubMed] [Google Scholar]
- Bix M., Raulet D. Functionally conformed free class I heavy chains exist on the surface of beta 2 microglobulin negative cells. J Exp Med. 1992 Sep 1;176(3):829–834. doi: 10.1084/jem.176.3.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bluestone J. A., Kaliyaperumal A., Jameson S., Miller S., Dick R., 2nd Peptide-induced changes in class I heavy chains alter allorecognition. J Immunol. 1993 Oct 15;151(8):3943–3953. [PubMed] [Google Scholar]
- Buchmeier M. J., Zinkernagel R. M. Immunodominant T cell epitope from signal sequence. Science. 1992 Aug 21;257(5073):1142–1142. doi: 10.1126/science.257.5073.1142. [DOI] [PubMed] [Google Scholar]
- Deverson E. V., Gow I. R., Coadwell W. J., Monaco J. J., Butcher G. W., Howard J. C. MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature. 1990 Dec 20;348(6303):738–741. doi: 10.1038/348738a0. [DOI] [PubMed] [Google Scholar]
- Esquivel F., Yewdell J., Bennink J. RMA/S cells present endogenously synthesized cytosolic proteins to class I-restricted cytotoxic T lymphocytes. J Exp Med. 1992 Jan 1;175(1):163–168. doi: 10.1084/jem.175.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glas R., Franksson L., Ohlén C., Höglund P., Koller B., Ljunggren H. G., Kärre K. Major histocompatibility complex class I-specific and -restricted killing of beta 2-microglobulin-deficient cells by CD8+ cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11381–11385. doi: 10.1073/pnas.89.23.11381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Hammond S. A., Bollinger R. C., Tobery T. W., Silliciano R. F. Transporter-independent processing of HIV-1 envelope protein for recognition by CD8+ T cells. Nature. 1993 Jul 8;364(6433):158–161. doi: 10.1038/364158a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Hosken N. A., Bevan M. J. An endogenous antigenic peptide bypasses the class I antigen presentation defect in RMA-S. J Exp Med. 1992 Mar 1;175(3):719–729. doi: 10.1084/jem.175.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iwabuchi K., Nakayama K., McCoy R. L., Wang F., Nishimura T., Habu S., Murphy K. M., Loh D. Y. Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9000–9004. doi: 10.1073/pnas.89.19.9000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobs H., Von Boehmer H., Melief C. J., Berns A. Mutations in the major histocompatibility complex class I antigen-presenting groove affect both negative and positive selection of T cells. Eur J Immunol. 1990 Oct;20(10):2333–2337. doi: 10.1002/eji.1830201024. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- Monaco J. J., Cho S., Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990 Dec 21;250(4988):1723–1726. doi: 10.1126/science.2270487. [DOI] [PubMed] [Google Scholar]
- 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]
- Nikolić-Zugić J., Bevan M. J. Role of self-peptides in positively selecting the T-cell repertoire. Nature. 1990 Mar 1;344(6261):65–67. doi: 10.1038/344065a0. [DOI] [PubMed] [Google Scholar]
- Pircher H., Brduscha K., Steinhoff U., Kasai M., Mizuochi T., Zinkernagel R. M., Hengartner H., Kyewski B., Müller K. P. Tolerance induction by clonal deletion of CD4+8+ thymocytes in vitro does not require dedicated antigen-presenting cells. Eur J Immunol. 1993 Mar;23(3):669–674. doi: 10.1002/eji.1830230315. [DOI] [PubMed] [Google Scholar]
- Powis S. J., Townsend A. R., Deverson E. V., Bastin J., Butcher G. W., Howard J. C. Restoration of antigen presentation to the mutant cell line RMA-S by an MHC-linked transporter. Nature. 1991 Dec 19;354(6354):528–531. doi: 10.1038/354528a0. [DOI] [PubMed] [Google Scholar]
- Rötzschke O., Falk K., Faath S., Rammensee H. G. On the nature of peptides involved in T cell alloreactivity. J Exp Med. 1991 Nov 1;174(5):1059–1071. doi: 10.1084/jem.174.5.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Shepherd J. C., Schumacher T. N., Ashton-Rickardt P. G., Imaeda S., Ploegh H. L., Janeway C. A., Jr, Tonegawa S. TAP1-dependent peptide translocation in vitro is ATP dependent and peptide selective. Cell. 1993 Aug 13;74(3):577–584. doi: 10.1016/0092-8674(93)80058-m. [DOI] [PubMed] [Google Scholar]
- Sijts A. J., De Bruijn M. L., Nieland J. D., Kast W. M., Melief C. J. Cytotoxic T lymphocytes against the antigen-processing-defective RMA-S tumor cell line. Eur J Immunol. 1992 Jun;22(6):1639–1642. doi: 10.1002/eji.1830220644. [DOI] [PubMed] [Google Scholar]
- Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., Pious D., DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. doi: 10.1038/348744a0. [DOI] [PubMed] [Google Scholar]
- Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A. Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. Nature. 1990 Dec 20;348(6303):741–744. doi: 10.1038/348741a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Yang Y., Früh K., Chambers J., Waters J. B., Wu L., Spies T., Peterson P. A. Major histocompatibility complex (MHC)-encoded HAM2 is necessary for antigenic peptide loading onto class I MHC molecules. J Biol Chem. 1992 Jun 15;267(17):11669–11672. [PubMed] [Google Scholar]
- Zhou X., Glas R., Liu T., Ljunggren H. G., Jondal M. Antigen processing mutant T2 cells present viral antigen restricted through H-2Kb. Eur J Immunol. 1993 Aug;23(8):1802–1808. doi: 10.1002/eji.1830230811. [DOI] [PubMed] [Google Scholar]
- Zhou X., Glas R., Momburg F., Hämmerling G. J., Jondal M., Ljunggren H. G. TAP2-defective RMA-S cells present Sendai virus antigen to cytotoxic T lymphocytes. Eur J Immunol. 1993 Aug;23(8):1796–1801. doi: 10.1002/eji.1830230810. [DOI] [PubMed] [Google Scholar]
- Zijlstra M., Auchincloss H., Jr, Loring J. M., Chase C. M., Russell P. S., Jaenisch R. Skin graft rejection by beta 2-microglobulin-deficient mice. J Exp Med. 1992 Apr 1;175(4):885–893. doi: 10.1084/jem.175.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zijlstra M., Bix M., Simister N. E., Loring J. M., Raulet D. H., Jaenisch R. Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature. 1990 Apr 19;344(6268):742–746. doi: 10.1038/344742a0. [DOI] [PubMed] [Google Scholar]
- Zweerink H. J., Gammon M. C., Utz U., Sauma S. Y., Harrer T., Hawkins J. C., Johnson R. P., Sirotina A., Hermes J. D., Walker B. D. Presentation of endogenous peptides to MHC class I-restricted cytotoxic T lymphocytes in transport deletion mutant T2 cells. J Immunol. 1993 Mar 1;150(5):1763–1771. [PubMed] [Google Scholar]