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An unexpectedly labile mitochondrially encoded protein is required for Mta expression

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Maternally transmitted antigen (Mta) is a mouse major histocompatibility antigen recognized by cytotoxic T lymphocytes. A role for mitochondria in expression of this class I-like cell surface antigen has been previously established. We now show that a labile product of mitochondrial protein synthesis is required for Mta expression. Reexpression of Mta determinants after enzymatic removal occurred within 24 h, and the regeneration process was sensitive to chloramphenicol (CAP), a selective inhibitor of mitochondrial protein synthesis. Additionally, target cells treated with CAP for as little as 18 h showed diminished expression of Mta. The estimated half-life for Mtf products ranged from 6 to 15 h, less than the half-lives of known mitochondrial translation products. This suggests that the Mtf product is not generated by the normal turnover of stable mitochondrial respiratory proteins. Instead, these results indicate the existence of either labile unknown mitochondrially encoded peptides or a rapid turnover pathway for known mitochondrial products.

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  1. Adorini, L., Muller, S., Cardinaux, F., Lehmann, P. V., Falcioni, F., and Nagy, Z. A.:In vivo competition between self peptides and foreign antigens in T-cell activation.Nature 334: 623–625, 1988

  2. Aldrich, C. J., Jenkins, R. N., and Rich, R. R.: Clonal analysis of the anti-Qa-1 cytotoxic T lymphocyte repertoire: definition of the Qa-Id and Qa-1c alloantigens and cross-reactivity with H-2.J Immunol 136: 383–388, 1986

  3. Bibb, M. J., Van Etten, R. A., Wright, C. T., Walberg, M. W., and Clayton, D. A.: Sequence and gene organization of mouse mitochondrial DNA.Cell 26: 167–180, 1981

  4. Bjorkman, P. J., Saper, M. A., Samraoui, B., Bennett, W. S., Strominger, J. L., and Wiley, D. C.: The foreign antigen binding site and T cell recognition regions of class 1 histocompatibility antigens.Nature 329: 512–518, 1987

  5. Brunner, K. T., Engers, H. D., and Cerottini, J. C.: The51Cr release assay as used for the quantitative measurement of cell-mediated cytolysisin vitro.In B. R. Bloom and J. R. David (eds.):In Vitro Methods in Cell-Mediated and Tumor Immunity, pp. 423–428, Academic Press, New York, 1976

  6. Craigen, W. J., Cook, R. G., Tate, W. P., and Caskey, C. T.: Bacterial peptide chain release factors: conserved primary structure and possible frameshift regulation of release factor 2.Proc Natl Acad Sci USA 82: 3616–3620, 1985

  7. Ehrlich, R., Maguire, J. E., and Singer, D. S.: Identification of negative and positive regulatory elements associated with a class I major histocompatibility complex gene.Mol Cell Biol 8: 695–703, 1988

  8. Eisenlohr, L. C., Gerhard, W., and Hackett, C. J.: Individual class IIrestricted antigenic determinants of the same protein exhibit distinct kinetics of appearance and persistence on antigen-presenting cells.J Immunol 141: 2581–2584, 1988

  9. Ferris, S. D., Ritte, U., Fischer Lindahl, K., Prager, E. M., and Wilson, A. C.: Unusual type of mitochondrial DNA in mice lacking a maternally transmitted antigen.Nucleic Acids Res 11: 2917–2926, 1983

  10. Fischer Lindahl, K., Hausmann, B., and Chapman, V. M.: A newH-2-linked class I gene whose expression depends on a maternally inherited factor.Nature 306: 383–385, 1983

  11. Fox, T. D. and Brummer, B. W.: Leaky +1 and −1 frameshift mutations at the same site in a yeast mitochondrial gene. Nature288: 60–63, 1980

  12. Garrod, L. P., Lambert, H. P., and O'Grady, F.: Chloramphenicol.In L. P. Garrod (ed.):Antibiotic and Chemotherapy, pp. 155–168, Churchill Livingstone, Edinburgh, 1981

  13. Han, A. C., Rodgers, J. R., and Rich, R. R.: Unglycosylated Mtaa expresses an Mtab-like determinant.Immunogenetics 25: 234–240, 1987

  14. Hare, J. F. and Hodges, R.: Turnover of mitochondrial inner membrane proteins in hepatoma monolayer cultures.J Biol Chem 257: 3575–3580, 1982

  15. Jenkins, R. N., Aldrich, C. J., Lopez, L. A., and Rich, R. R.: Oligosaccharide-dependent and independent Qa-1 determinants.J Immunol 134: 3218–3225, 1985

  16. Kaneko, T., Watanabe, T., and Oishi, M.: Effect of mitochondrial protein synthesis inhibitors on erythroid differentiation of mouse erythro-leukemia (Friend) cells.Mol Cell Biol 8: 3311–3315, 1988

  17. Knecht, E., Hernandez-Yago, J., Martinez-Ramon, A., and Grisolia, S.: Fate of proteins synthesized in mitochondria of cultured mammalian cells revealed by electron microscope radioautography.Exp Cell Res 125: 91–199, 1980

  18. Landolfi, N. F., Rich, R. R., and Cook, R. G.: Differential glycosylation requirements for the cell surface expression of class I molecules.J Immunol 134: 423–430, 1985

  19. Mellman, I., Fuchs, R., and Helenius, A.: Acidification of the endocytic and exocytic pathways.Annu Rev Biochem 55: 663–700, 1986

  20. Pestka, S.: Inhibitors of protein synthesis.In H. Weissbach and S. Pestka (eds.):Molecular Mechanisms of Protein Biosynthesis, pp. 467–553, Academic Press, New York, 1977

  21. Rodgers, J. R., Smith, R., III, Huston, M. M., and Rich, R. R.: Maternally transmitted antigen.Adv Immunol 38: 313–359, 1986

  22. Shaw, J. M., Feagin, J. E., Stuart, K., and Simpson, L.: Editing of kineto plastid mitochondrial mRNAs by uridine addition and deletion generates conserved amino acid sequences and AUG initiation codons.Cell 53: 401–411, 1988

  23. Shirayoshi, Y., Miyazaki, J. I., Burke, P. A., Hamada, K., Appella, E., and Ozato, K.: Binding of multiple nuclear factors to the 5' upstream regulatory element of the murine major histocompatibility class I gene.Mol Cell Biol 7: 4542–4548, 1987

  24. Smith, R., III and Rich, R. R.: Polymorphism and tissue distribution of maternally transmitted antigen defined by cytotoxic T lymphocyte lines.J Immunol 134: 2191–2197, 1985

  25. Smith, R., III, Huston, M. M., Jenkins, R. N., Huston, D. P., and Rich, R. R.: Mitochondria control expression of a murine cell surface antigen.Nature 306: 599–601, 1983

  26. Song, E. S., Linsk, R., Olson, C. A., McMillan, M., and Goodenow, R. S.: Allospecific cytotoxic T lymphocytes recognize an H-2 peptide in the context of a murine major histocompatibility complex class I molecule.Proc Natl Acad Sci USA 85: 1927–1931, 1988

  27. Townsend, A. R. M., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D., and McMichael, A. J.: The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides.Cell 44: 959–968, 1986

  28. Townsend, A., Bastin, J., Gould, K., Brownlee, G., Andrew, M., Coupar, B., Boyle, D., Chan, S., and Smith, G.: Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia infected cells is overcome by enhanced degradation of antigen.J Exp Med 168: 1211–1224, 1988

  29. Tzagoloff, A., Macino, G., and Sebald, W.: Mitochondrial genes and translation products.Annu Rev Biochem 48: 419–441, 1979

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Correspondence to Robert R. Rich.

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Han, A.C., Rodgers, J.R. & Rich, R.R. An unexpectedly labile mitochondrially encoded protein is required for Mta expression. Immunogenetics 29, 258–264 (1989). https://doi.org/10.1007/BF00717910

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  • Chloramphenicol
  • Surface Antigen
  • Selective Inhibitor
  • Mitochondrial Respiratory
  • Cell Surface Antigen