An endogenous antigenic peptide bypasses the class I antigen presentation defect in RMA-S.
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.
Hosken
N A
NA
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Bevan
M J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002459:Cell Fusion; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology; D009975:Orthomyxoviridae / Q000276:immunology; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus; D014764:Viral Proteins / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D009698:Nucleoproteins; D014764:Viral Proteins