Abstract
The RMA-S cell line was derived from the Raucher virus-induced murine cell line RBL-5 by ethylmethane sulfonate mutagenesis and anti-H-2 antibody plus complement selection (Ljunggren, H.-G., and K. Karre. 1985. J. Exp. Med. 162:1745). RMA-S is defective in the ability to present endogenously synthesized antigens to class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443; Ohlen, C., J. Bastin, H.- G. Ljunggren, L. Foster, E. Wolpert, G. Klein, A. R. M. Townsend, and K. Karre. 1990. J. Immunol. 145:52). This defect has been attributed to the inability of RMA-S to deliver antigenic peptides derived from antigens in the cytosol into the endoplasmic reticulum (ER), where they can associate with class I MHC molecules (Townsend, A., C. Ohlen, J. Bastin, H.-G. Ljunggren, L. Foster, and K. Karre. 1989. Nature [Lond.]. 340:443). We show that RMA-S can present at least one endogenous antigen, vesicular stomatitis virus nucleoprotein (VSV-N), to class I MHC-restricted CTL. RMA-S presents VSV-N to CTL both when infected with VSV or transfected with the VSV nucleoprotein gene. The natural antigenic VSV nucleoprotein peptides purified from either RMA or RMA-S are indistinguishable when analyzed by high performance liquid chromatography. We also show that the genetic defect responsible for the RMA-S phenotype maps to the murine chromosome 17. This chromosome encodes the murine class I MHC genes as well as two genes, HAM-1 and - 2, with homology to the adenosine triphosphate-dependent transporter superfamily (Monaco, J. J., S. Cho, and M. Attaya. 1990. Science [Wash. DC]. 250:1723). These results suggest that the system that delivers antigenic peptides from the cytosol to the ER in RMA-S may still be present and retain partial function.
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- Bevan M. J. Antigen recognition. Class discrimination in the world of immunology. Nature. 1987 Jan 15;325(6101):192–194. doi: 10.1038/325192b0. [DOI] [PubMed] [Google Scholar]
- Burgert H. G., White J., Weltzien H. U., Marrack P., Kappler J. W. Reactivity of V beta 17a+ CD8+ T cell hybrids. Analysis using a new CD8+ T cell fusion partner. J Exp Med. 1989 Dec 1;170(6):1887–1904. doi: 10.1084/jem.170.6.1887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carbone F. R., Bevan M. J. Induction of ovalbumin-specific cytotoxic T cells by in vivo peptide immunization. J Exp Med. 1989 Mar 1;169(3):603–612. doi: 10.1084/jem.169.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cerundolo V., Alexander J., Anderson K., Lamb C., Cresswell P., McMichael A., Gotch F., Townsend A. Presentation of viral antigen controlled by a gene in the major histocompatibility complex. Nature. 1990 May 31;345(6274):449–452. doi: 10.1038/345449a0. [DOI] [PubMed] [Google Scholar]
- Cho S., Attaya M., Brown M. G., Monaco J. J. A cluster of transcribed sequences between the Pb and Ob genes of the murine major histocompatibility complex. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5197–5201. doi: 10.1073/pnas.88.12.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeMars R., Rudersdorf R., Chang C., Petersen J., Strandtmann J., Korn N., Sidwell B., Orr H. T. Mutations that impair a posttranscriptional step in expression of HLA-A and -B antigens. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8183–8187. doi: 10.1073/pnas.82.23.8183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erlich H., Lee J. S., Petersen J. W., Bugawan T., DeMars R. Molecular analysis of HLA class I and class II antigen loss mutants reveals a homozygous deletion of the DR, DQ, and part of the DP region: implications for class II gene order. Hum Immunol. 1986 Jun;16(2):205–219. doi: 10.1016/0198-8859(86)90049-2. [DOI] [PubMed] [Google Scholar]
- Gallione C. J., Greene J. R., Iverson L. E., Rose J. K. Nucleotide sequences of the mRNA's encoding the vesicular stomatitis virus N and NS proteins. J Virol. 1981 Aug;39(2):529–535. doi: 10.1128/jvi.39.2.529-535.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Germain R. N. Immunology. The ins and outs of antigen processing and presentation. Nature. 1986 Aug 21;322(6081):687–689. doi: 10.1038/322687a0. [DOI] [PubMed] [Google Scholar]
- Hosken N. A., Bevan M. J. Defective presentation of endogenous antigen by a cell line expressing class I molecules. Science. 1990 Apr 20;248(4953):367–370. doi: 10.1126/science.2326647. [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]
- Moore M. W., Carbone F. R., Bevan M. J. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. doi: 10.1016/s0092-8674(88)91043-4. [DOI] [PubMed] [Google Scholar]
- Morrison L. A., Lukacher A. E., Braciale V. L., Fan D. P., Braciale T. J. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 1;163(4):903–921. doi: 10.1084/jem.163.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohlén C., Bastin J., Ljunggren H. G., Foster L., Wolpert E., Klein G., Townsend A. R., Kärre K. Resistance to H-2-restricted but not to allo-H2-specific graft and cytotoxic T lymphocyte responses in lymphoma mutant. J Immunol. 1990 Jul 1;145(1):52–58. [PubMed] [Google Scholar]
- Ohlén C., Bastin J., Ljunggren H. G., Imreh S., Klein G., Townsend A. R., Kärre K. Restoration of H-2b expression and processing of endogenous antigens in the MHC class I pathway by fusion of a lymphoma mutant to L cells of the H-2k haplotype. Eur J Immunol. 1990 Aug;20(8):1873–1876. doi: 10.1002/eji.1830200837. [DOI] [PubMed] [Google Scholar]
- Puddington L., Bevan M. J., Rose J. K., Lefrançois L. N protein is the predominant antigen recognized by vesicular stomatitis virus-specific cytotoxic T cells. J Virol. 1986 Nov;60(2):708–717. doi: 10.1128/jvi.60.2.708-717.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rötzschke O., Falk K., Wallny H. J., Faath S., Rammensee H. G. Characterization of naturally occurring minor histocompatibility peptides including H-4 and H-Y. Science. 1990 Jul 20;249(4966):283–287. doi: 10.1126/science.1695760. [DOI] [PubMed] [Google Scholar]
- Salter R. D., Cresswell P. Impaired assembly and transport of HLA-A and -B antigens in a mutant TxB cell hybrid. EMBO J. 1986 May;5(5):943–949. doi: 10.1002/j.1460-2075.1986.tb04307.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salter R. D., Howell D. N., Cresswell P. Genes regulating HLA class I antigen expression in T-B lymphoblast hybrids. Immunogenetics. 1985;21(3):235–246. doi: 10.1007/BF00375376. [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]
- Spies T., DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991 May 23;351(6324):323–324. doi: 10.1038/351323a0. [DOI] [PubMed] [Google Scholar]
- Sprague J., Condra J. H., Arnheiter H., Lazzarini R. A. Expression of a recombinant DNA gene coding for the vesicular stomatitis virus nucleocapsid protein. J Virol. 1983 Feb;45(2):773–781. doi: 10.1128/jvi.45.2.773-781.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Townsend A. R., Gotch F. M., Davey J. Cytotoxic T cells recognize fragments of the influenza nucleoprotein. Cell. 1985 Sep;42(2):457–467. doi: 10.1016/0092-8674(85)90103-5. [DOI] [PubMed] [Google Scholar]
- Townsend A. R., Rothbard J., Gotch F. M., Bahadur G., Wraith D., McMichael A. J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986 Mar 28;44(6):959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
- Townsend A., Ohlén C., Bastin J., Ljunggren H. G., Foster L., Kärre K. Association of class I major histocompatibility heavy and light chains induced by viral peptides. Nature. 1989 Aug 10;340(6233):443–448. doi: 10.1038/340443a0. [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 Bleek G. M., Nathenson S. G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990 Nov 15;348(6298):213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]