Abstract
Human complement component C4 is encoded by two HLA-linked loci, A and B. In the mouse, the H-2 region contains structural genes for two serum proteins that react with antibodies to human C4, but one of these proteins (Slp) has no C4 hemolytic activity. Because the product of C4-A locus in man has low hemolytic activity, a previous report suggests it may be the homologue of murine Slp. We show here that Slp antigenic determinants are found in human C4. However, they are expressed in the products of both loci A and B, that is, C4A and C4B, since both proteins were specifically immunoprecipitated by the IgG fraction of alloantisera to mouse Slp. Therefore, Slp-associated structural features are preserved in evolution, although they do not seem to be relevant to the hemolytic properties of C4.
Similar content being viewed by others
References
Awdeh, Z. L., Raum, D., and Alper, C. A.: Genetic polymorphism of human complement C4 and detection of heterozygotes. Nature 282: 205–207, 1979
Awdeh, Z. L. and Alper, C.: Inherited structural polymorphism of the fourth component of human complement. Proc. Natl. Acad. Sci. U.S.A. 77: 3576–3580, 1980
Carroll, M. C. and Capra, J. D.: Studies on murine Ss protein: Demonstration that S region encodes structural gene for the fourth component of complement. Proc. Natl. Acad. Sci. U.S.A. 76: 4641–4645, 1979
Chan, A. C., Mitchell, K. R., Munns, T. W., Karp, D. R., and Atkinson, J. P.: Identification and partial characterization of the secreted form of the fourth component of human complement: evidence that it is different from the major plasma form. Proc. Natl. Acad. Sci. U.S.A. 80: 268–272, 1983
Chu, V. F. H., March, W. L., and Gigli, I.: Chido and Rodgers antigenic determinants on the fourth component of human complement. J. Immunol. 128: 181–185, 1982
Ferreira, A. and Nussenzweig, V.: Mouse C4 (Ss): Three-step purification of its C4c fragment and production of monospecific antiserum. J. Immunol. 122: 490–493, 1979
Ferreira, A., Michaelson, J., and Nussenzweig, V.: A polymorphism of the γ chain of mouse C4 controlled by the S region of the major histocompatibility complex. J. Immunol. 125: 1178–1182, 1980a
Ferreira, A., Michaelson, J., and Nussenzweig, V.: H-2-controlled polymorphism of the γ chain of Slp (sex-limited protein). Immunogenetics 11: 491–497, 1980b
Ferreira, A., David, C. S., and Nussenzweig, V.: The murine H-2.7 specificity is an antigenic determinant of C4d, a fragment of the fourth component of the complement system. J. Exp. Med. 151: 1424–1435, 1980c
Ferreira, A., Nussenzweig, V., and Gigli, I.: Structural and functional differences between the H-2 controlled Ss and Slp proteins. J. Exp. Med. 148: 1186–1197, 1978
Ferreira, A., Eichinger, D., and Nussenzweig, V.: The murine sex-limited protein (Slp): reassessment of its sex limitation. J. Immunol. 129: 1506–1508, 1982
Gigli, I.: A single chain precursor of C4 in human serum. Nature 272: 836–837, 1978
Gorski, J. P. and Muller-Eberhard, H. J.: Single chain C4 from human plasma. J. Immunol. 120: 1775, 1978
Hansen, T. H., Krasteff, T. N., and Shreffler, D. C.: Quantitative variations in the expression of the mouse serum antigens Ss and its sex-limited allotype Slp. Biochem. Genet. 12: 281–293, 1974
Huang, C. M. and Klein, J.: Murine antigen H-2.7: Localization of its antigenic determinant to the Ss (C4) molecule. Immunogenetics 11: 605–615, 1980
Klein, J.: A case of no sex-limitation of Slp in the murine H-2 complex. Immunogenetics 2: 297–299, 1975
Laemmli, J. K.: Cleavage of structural. proteins during the assembly of the head of bacteriophage T4, Nature 227: 680–685, 1970
Natsuume-Sakai, S., Kaido, T., Nonaka, M., Omano, S., and Takahashi, M.: Structural polymorphism of murine C4 and its linkage to H-2. J. Immunol. 124: 2714–2720, 1980
O'Neill, G. J., Yang, S. Y., Tegoli, J., Berger, R., and Dupont, B.: Chido and Rodgers blood groups are distinct antigenic components of human complement C4. Nature 273: 668–670, 1978a
O'Neill, G. J., Yang, S. Y., and Dupont, B.: Two HLA-linked loci controlling the fourth component of human complement. Proc. Natl. Acad. Sci. U.S.A. 75: 5165–5169, 1978b
Parker, K. L., Roos, M. H., and Shreffler, D. C.: Structural characterization of the murine fourth component of complement and sex-limited protein and their precursors: evidence for two loci in the S region of the H-2 complex. Proc. Natl. Acad. Sci. U.S.A. 76: 5853–5557, 1979
Passmore, H. C.: An erythrocyte and serum antigen with a specificity, antithetical to the mouse C4 associated H-2.7 antigen. J. Immunol. 128: 2559–2562, 1982
Passmore, H. C. and Biesel, K. W.: Preparation of antisera for the detection of the Ss protein and the Slp alloantigen. Immunogenetics 4: 393–399, 1977
Passmore, H. C. and Shreffler, D. C.: A sex-limited serum protein variant in the mouse: Inheritance and association with the H-2 region. Biochem. Genet. 4: 351–365, 1970
Roos, M. H., Atkinson, J. P., and Shreffler, D. C.: Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: subunit composition, chain size polymorphism, and an intracellular (PRO-Ss) precursor. J. Immunol. 121: 1106–1115, 1978
Roos, M. H., Mollenhauer, E., Démant, P., and Rittner, C.: A molecular basis for the two locus model of human complement component C4. Nature 298: 854–856, 1982
Schenkein, I., Lavy, M., and Uhr, J.: The use of glucose oxidase as a generator of H2O2 in the enzymatic radioiodination of components of cell surfaces. Cell. Immunol. 5: 490–493, 1972
Spinella, D. G., and Passmore, H.: A newly defined murine alloantigen controlled by the S region of the H-2 complex: molecular association with the fourth component of complement. J. Immunol. 130: 824–828, 1983
Tack, B. F., Janatova, J., Thomas, M. L., Harrison, R. A., and Hammer, C. H.: The third, fourth, and fifth components of human complement: isolation and biochemical properties. Methods Enzymol. 80: 64–101, 1981
Tilley, C. A., Romans, D. G., and Crookston, M. C.: Localization of Chido and Rodgers determinants to the C4d fragment of human C4. Nature 276: 713–715, 1978
Vergara, U.: Mouse Slp: female expression due to a dominant non-H-2 gene in wild mice. Immunogenetics 15: 601–604, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ferreira, A., Nussenzweig, V. Murine sex-limited protein (Slp) antigenic sites in human complement component C4. Immunogenetics 18, 335–341 (1983). https://doi.org/10.1007/BF00372466
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00372466