Genetic Control and Intersite Influences on the Immune Response to Sperm Whale Myoglobin
- 32 Downloads
Determination of the precise antigenic structure of sperm-whale myoglobin (Mb) has enabled us to focus our attention on the molecular and cellular factors that control and regulate the immune responses to the protein antigen. Our studies have shown that the immune responses to sperm-whale Mb are controlled by genes in the I region of the major histocompatibility complex (H-2) of mice. More importantly, the responses to the synthetic antigenic sites are each under separate genetic control. The recognition of the antigenic sites by antibodies is independent of the immunized species and of the time the antisera are obtained after the initial immunization (from nine days up to a year). The same sites are recognized by antisera raised in rabbit, goat, pig, cat, chicken and outbred and inbred mice. The same sites recognized by mouse B-cells are also recognized by mouse T-cells. No meaningful genetic control of antibody affinity was observed. Autoimmune antibody and T-lymphocyte proliferative responses were readily generated by immunizing an animal with self-Mb. With mouse Mb, the autoimmune T-lymphocyte response was under genetic control and mapped with the I-A and the H-2D end of the H-2 gene complex. In other recent studies we have shown, using several Mb variants, that the binding capacity of an antigenic site is fully accounted for by substitutions in the antigenic sites (actual contact residues) and in residues close (within 7.Å) to the sites (i.e. environmental residues). The overall response to Mb is regulated by inter-site influences which can either be of a cooperative (help) nature or of a suppressive nature. Finally, genetic control of the responses to individual antigenic sites on a protein is not only determined by the genetic constitution of the host but also by the chemical properties of the individual sites. The H-2 subregions mapping the responses to given antigenic sites can also recognize other sites, which were previously unrecognizable in a homologous protein, if the chemical properties of these sites are suitably altered.
KeywordsGenetic Control Killer Whale Antigenic Site Congenic Strain High Responder
immune response gene
the major histocompatibility complex
0.01 M sodium phosphate buffer, pH 7.2, containing 0.15 M NaCl.
Unable to display preview. Download preview PDF.
- 9.S.S. Twining, C.S. David and M.Z. Atassi, Genetic control of the immune response to myoglobin. IV. Mouse antibodies in outbred and congenic strains against sperm-whale myoglobin recognize the same antigenic sites that are recognized by antibodies raised in other species. Mol. Immunol. 18: 447 (1981).PubMedCrossRefGoogle Scholar
- 12.S.S. Twining, H. Lehmann and M.Z. Atassi, The antibody response to myoglobin is independent of the immunized species: Analysis in terms of replacements in the antigenic sites and in environmental residues of the cross-reactions of fifteen myoglobins with sperm-whale myoglobin antisera raised in different species. Biochem. J. 191: 681 (1980).PubMedGoogle Scholar
- 17.M.Z. Atassi and A.L. Kazim, First consequences of the determination of the entire antigenic structure of sperm-whale myoglobin in “Immunobiology of Proteins and Peptides” (Atassi, M.Z. and Stavitsky, A.B., Eds.) Vol. 1, pp. 19–40, Plenum Press, New York, NY.Google Scholar
- 21.S. Sakata and M.Z. Atassi, Autorecognition of serum albumin. Fed. Proc. 39, Abstr. 3428 (1980).Google Scholar
- 28.M.Z. Atassi, S.S. Twining, H. Lehmann and C.S. David, Genetic control of the immune response to myoglobin. V. Analysis of the cross-reactivity of 12 myoglobins with sperm-whale myoglobin antisera of inbred mouse strains in terms of substitutions in the antigenic sites and in the environmental residues of the sites. Immunol. Commun. 10: 359 (1981).PubMedGoogle Scholar
- 31.M.Z. Atassi, S. Yokota, S.S. Twining, H. Lehmann and C.S. David, Genetic control of the immune response to myoglobin. VI. Inter-site influences in T-lymphocyte proliferative response from analysis of cross-reactions of ten myoglobins in terms of substitutions in the antigenic sites and in environmental residues of the sites. Mol. Immunol. 18: 945 (1981).PubMedCrossRefGoogle Scholar
- 34.C.R. Young, G.P. O’Connor and M.Z. Atassi, Genetic control of the immune response to myoglobin. VII. Antibody responses to myoglobin variants reveal that gene restriction of the antibody responses to myoglobin antigenic sites is dependent on the chemical properties of the sites. Immunol. Commun. 10: 483 (1981).PubMedGoogle Scholar