Abstract
The genetic and molecular requirements for cell-surface expression of Ia antigens precipitated by anti-I-E subregion sera have been examined. Inbred mice of thed, k, p, andr haplotypes synthesize and express on their lymphocytes the two I-region products normally found in anti-I-E-subregion immunoprecipitates, E α and Ae (E β ). Cells from mice of theb ands haplotypes fail to synthesize E α chains but do synthesize Ae chains, which remain in the cytoplasm as partially glycosylated precursors. Cells of thef andq haplotypes fail to synthesize either the Ae or E α polypeptide chains, as shown by both genetic complementation tests and analyses of total cell proteins by two-dimensional polyacrylamide gel electrophoresis. The patterns of expression of the intact E α :Ae complex are consistent with the theory that both the Ae and E α polypeptide chains must be present in the cells for either chain to be expressed in normal amounts on the cell surface. The implications of these observations for the genetics ofI-region-controlled functions are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Benacerraf, B. and Dorf, M. E.: Genetic control of specific immune responses and immune suppressions byI-region genes.Cold Spring Harbor Symp. Quant. Biol. 41; 465–475, 1976
Cook, R. G., Uhr, J. W., Vitetta, E. S., and Capra, J. D.: Structural studies on the murine Ia alloantigens. III. Tryptic peptide comparisons of allelic products of theI-E/C subregion.Mol. Immunol. 16: 29–35, 1979 a
Cook, R. G., Vitetta, E. S., Uhr, J. W., and Capra, J. D.: Structural studies on the murine Ia alloantigens. V. Evidence that the structural gene for theI-E/C beta polypeptide is encoded within theI-A subregion.J. Exp. Med. 149: 13–18, 1979b
David, C. S., Cullen, S. E., and Murphy, D. B.: Serologic and biochemical studies with the H-2 gene complex of mice. Further evidence for theI-C subregion.J. Immunol. 114: 1205–1209, 1975
David, C. S. and Cullen, S. E.: Murine Ia antigens: identification and mapping of Ia.23 and further definition of theI-E subregion.J. Immunol. 120: 1659–1662, 1978
Duncan, W. R., Wakeland, E. K., and Klein, J.: Histocompatibility-2 system in wild mice. VIII. Frequencies of H-2 and Ia antigens in wild mice from Texas.Immunogenetics 9: 261–272, 1979
Frelinger, J. A., Niederhuber, J., David, C. S., and Shreffler, D. C.: Inhibition of immune responsesin vitro by specific antiserums to Ia antigens.Science 188: 268–270, 1975
Götze, D., Nadeau, J., Wakeland, E. K., Berry, R. J., Bonhomme, F., Egorov, I. K., Hjorth, J. P., Hoogstraal, H., Vives, J., Winking, H., and Klein, J.: Histocompatibility-2 system in wild mice. X. Frequencies of H-2 and Ia antigens in wild mice from Europe and Africa.J. Immunol. 124: 2675–2681, 1980
Harris, J. F. and Delovitch, T. L.: Derivation of monoclonal antibody which detects an Ia antigen encoded by two complementing I-subregions.J. Immunol., in press, 1980
Jones, P. P.: Analysis of H-2 and Ia molecules by two-dimensional gel electrophoresis.J. Exp. Med. 146: 1261–1279, 1977
Jones, P. P., Murphy, D. B., and McDevitt, H. O.: Two-gene control of the expression of a murine Ia antigen.J. Exp. Med. 148: 925–939, 1978
Jones, P.P., Murphy, D. B., Hewgill, D., and McDevitt, H. O.: Detection of a common polypeptide chain inI-A andI-E subregion immunoprecipitates.Mol. Immunol. 16: 51–60, 1979
Jones, P. P.: Analysis of radiolabeled lymphocyte proteins by one and two-dimensional polyacrylamide gel electrophoresis.In B. Mishell and S. Shiigi (eds.):Selected Methods in Cellular Immunology, pp. 398–440, W. H. Freeman and Co., San Francisco, 1980
Klein, J., Merryman, C. F., Maurer, P. H., Hauptfeld, M., and Gardner, M. B.: Histocompatibility-2 System of wild mice. IV. Ia and Ir typing of two wild mouse populations.Cold Spring Harbor Symp. Quant. Biol. 41: 457–463, 1976
Klein, J., Flaherty, L., VandeBerg, J. L., and Shreffler, D. C.:H-2 haplotypes, genes, regions, and antigens: first listing.Immunogenetics 6: 489–512, 1978
Klein, J.: The major histocompatibility complex of the mouse.Science 203: 516–521, 1979
Lafuse, W. P., McCormick, J. F., and David, C. S.: Serological and biochemical identification of hybrid Ia antigens.J. Exp. Med., in press, 1980 a
Lafuse, W. P., Neely, B. C., and David, C. S.: Biochemical characterization of murine Ia antigens with xenoantisera. I. Identification of a second Ia molecule (I-E?) inH-2 s haplotype.Immunogenetics 10: 311–318, 1980b
Lerner, E. A., Matis, L. A., Janeway, C. A., Jones, P. P., Schwartz, R. H., and Murphy, D. B.: A monoclonal antibody against an immune response (IR) gene product:J. Exp. Med., in press, 1980
McMillan, M., Cecka, J. M., Murphy, D. B., McDevitt, H. O., and Hood, L.: Structure of murine Ia antigens: Partial N-terminal amino acid sequences of products of the I-E/I-C subregion.Proc. Natl. Acad. Sci. U.S.A. 74: 5135–5139, 1977
Murphy, D. P., Jones, P. P., and McDevitt, H. O.: Serological analysis of recombinant strain A.TFR5.In H. O. McDevitt (ed.):Ir Genes and Ia Antigens, pp. 37–48, Academic Press, New York, 1978
Murphy, D. B.: Genetic fine structure of the H-2 gene complex.In M. E. Dorf (ed.):Role of the Major Histocompatibility Complex in Immunobiology, Garland Publishing, New York, in press, 1980
Murphy, D. B., Jones, P. P., Loken, M. R., and McDevitt, H. O.: Interaction betweenI-region loci influences the expression of a cell surface Ia antigen.Proc. Natl. Acad. Sci. U.S.A., in press, 1980
O'Farrell, P. H.: High resolution two-dimensional electrophoresis of proteins.J. Biol. Chem. 250: 4007–4021, 1975
O'Farrell, P. Z., Goodman, H. M., and O'Farrell, P. H.: High resolution two-dimensional electrophoresis of basic as well as acidic proteins.Cell 12: 1133–1141, 1977
Ozato, K., Lunney, J. K., El-Gamil, M., and Sachs, D. H.: Evidence for the absence of I-E/C antigen expression on the cell surface in mice of theH-2 b orH-2 s haplotypes.J. Immunol. 125: 940–945, 1980
Schwartz, R. H., David, C. S., Sachs, D. H., and Paul, W. E.: T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte proliferation with anti-Ia antisera.J. Immunol. 117: 531–540, 1976
Schwartz, R. H., Yano, A., Stimpfling, J. H., and Paul, W. E.: Gene complementation in the proliferative response to poly (Glu56Lys36Phe9)n. A demonstration that both immune response gene products must be expressed on the same antigen-presenting cell.J. Exp. Med. 149: 40–57, 1979
Shreffler, D. C., David, C. S., Cullen, S. E., Frelinger, J. A., and Niederhuber, J. E.: Serological and functional evidence for further subdivision of theI regions of theH-2 gene complex.Cold Spring Harbor Symp. Quant. Biol. 41: 477–487, 1976
Silver, J. and Russel, W. A.: Structural polymorphism ofI-E subregion antigens determined by a gene in the H-2K to I-B genetic interval.Nature 279: 437–439, 1979
Solinger, A. M., Ultee, M. E., Margoliash, E., and Schwartz, R. H.: T lymphocyte response to cytochrome c. I. Demonstration of a T-cell heteroclitic proliferative response and identification of a topographic antigenic determinant on pigeon cytochrome c whose immune recognition requires two comple-menting major histocompatibility complex-linked immune response genes.J. Exp. Med. 150: 830–848, 1979
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jones, P.P., Murphy, D.B. & McDevitt, H.O. Variable synthesis and expression of E β and A e (E β ) Ia polypeptide chains in mice of differentH-2 haplotypes. Immunogenetics 12, 321–337 (1981). https://doi.org/10.1007/BF01561674
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01561674