Abstract
The possibility was investigated that Ir genes regulate the function of cells other than T or B cells in the primary IgM responses to the synthetic antigens trinitrophenylated poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys [TNP-(T,G)-A--L]and trinitrophenylated poly-,-(His,Glu)-poly-D, L-Ala--poly-L-Lys [TNP-(H,G)-A--L]. The primary responses of (B10 × B10.A)F(1) spleen cells to both antigens were abrogated by Sephadex G-10 passage, and restored by the addition of spleen adherent cells. The cell type in the spleen adherent cell population active in reconstituting the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L was a non-T, non-B, radiation-resistant, glass-adherent spleen cell. The responses of Sephadex G-10-passed (responder x nonresponder)F(1) spleen cells to TNP-(T,G)-A--L or TNP-(H,G)-A--L were reconstituted by spleen adherent cells from only responder strains. Spleen adherent cells from F(1) mice reconstituted the responses to both antigens. Spleen adherent cells from each of the strains tested reconstituted the non- Ir gene-controlled response to a third antigen, TNP-keyhole limpet hemocyanin. The inability of spleen adherent cells from nonresponder strains to reconstitute the responses to either TNP-(T,G)-A--L or TNP-(H,G)-A--L was not a result of active suppression induced by the presence of nonresponder adherent cells, since a mixture of responder and nonresponder spleen adherent cells reconstituted the responses to both antigens. The use of spleen adherent cells from recombinant strains demonstrated that the autosomal dominant genes controlling the ability of spleen adherent cells to function as accessory cells in the responses to TNP-(T,G)-A--L and TNP-(H,G)-A--L are located in the K or I-A regions of the responder H-2 complex, the same region(s) of H-2 as the Ir genes controlling overall in vitro and in vivo responsiveness to these antigens.
Full Text
The Full Text of this article is available as a PDF (752.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barcinski M. A., Rosenthal A. S. Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells. J Exp Med. 1977 Mar 1;145(3):726–742. doi: 10.1084/jem.145.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benacerraf B., Katz D. H. The histocompatibility-linked immune response genes. Adv Cancer Res. 1975;21:121–173. doi: 10.1016/s0065-230x(08)60972-0. [DOI] [PubMed] [Google Scholar]
- Cowing C., Schwartz B. D., Dickler H. B. Macrophage Ia antigens. I. macrophage populations differ in their expression of Ia antigens. J Immunol. 1978 Feb;120(2):378–384. [PubMed] [Google Scholar]
- Hodes R. J., Singer A. Cellular and genetic control of antibody responses in vitro. I. Cellular requirements for the generation of genetically controlled primary IgM responses to soluble antigens. Eur J Immunol. 1977 Dec;7(12):892–897. doi: 10.1002/eji.1830071214. [DOI] [PubMed] [Google Scholar]
- Isac R., Mozes E. Antigen-specific T cell factors: a fine analysis of specificity. J Immunol. 1977 Feb;118(2):584–588. [PubMed] [Google Scholar]
- Kapp J. A., Pierce C. W., Benacerraf B. Genetic control of immune responses in vitro. II. Cellular requirements for the development of primary plaque-forming cell responses to the random terpolymer 1-glutamic acid 60-1-alanine30-1-tyrosine10 (GAT) by mouse spleen cells in vitro. J Exp Med. 1973 Nov 1;138(5):1121–1132. doi: 10.1084/jem.138.5.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lichtenberg L., Mozes E., Shearer G. M., Sela M. The role of thymus cells in the immune response to poly(Tyr, Glu)-polyD L Ala--polyLys as a function of the genetic constitution of the mouse strain. Eur J Immunol. 1974 Jun;4(6):430–434. doi: 10.1002/eji.1830040609. [DOI] [PubMed] [Google Scholar]
- Loken M. R., Herzenber L. A. Analysis of cell populations with a fluorescence-activated cell sorter. Ann N Y Acad Sci. 1975 Jun 30;254:163–171. doi: 10.1111/j.1749-6632.1975.tb29166.x. [DOI] [PubMed] [Google Scholar]
- Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
- McDevitt H. O., Deak B. D., Shreffler D. C., Klein J., Stimpfling J. H., Snell G. D. Genetic control of the immune response. Mapping of the Ir-1 locus. J Exp Med. 1972 Jun 1;135(6):1259–1278. doi: 10.1084/jem.135.6.1259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDevitt H. O. Genetic control of the antibody response. 3. Qualitative and quantitative characterization of the antibody response to (T,G)-A--L in CBA and C57 mice. J Immunol. 1968 Mar;100(3):485–492. [PubMed] [Google Scholar]
- Mitchell G. F., Grumet F. C., McDevitt H. O. Genetic control of the immune response. The effect of thymectomy on the primary and secondary antibody response of mice to poly-L(tyr, glu)-poly-D, L-ala--poly-L-lys. J Exp Med. 1972 Jan;135(1):126–135. doi: 10.1084/jem.135.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ordal J. C., Grumet F. C. Genetic control of the immune response. The effect of graft-versus-host reaction on the antibody response to poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys in nonresponder mice. J Exp Med. 1972 Nov 1;136(5):1195–1206. doi: 10.1084/jem.136.5.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierce C. W., Germain R. N., Kapp J. A., Benacerraf B. Secondary antibody responses in vitro to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by (responder X nonresponder)F1 spleen cells stimulated by parental GAT-macrophages. J Exp Med. 1977 Dec 1;146(6):1827–1832. doi: 10.1084/jem.146.6.1827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shevach E. M., Rosenthal A. S. Function of macrophages in antigen recognition by guinea pig T lymphocytes. II. Role of the macrophage in the regulation of genetic control of the immune response. J Exp Med. 1973 Nov 1;138(5):1213–1229. doi: 10.1084/jem.138.5.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singer A., Dickler H. B., Hodes R. J. Cellular and genetic control of antibody responses in vitro. II. Ir gene control of primary IgM responses to trinitrophenyl conjugates of poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys and poly-L-(His,Glu)-poly-D,L-Ala--poly-L-Lys. J Exp Med. 1977 Oct 1;146(4):1096–1107. doi: 10.1084/jem.146.4.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taussig M. J., Munro A. J. Antigen-specific T-cell factor in cell cooperation and genetic control of the immune response. Fed Proc. 1976 Jul;35(9):2061–2066. [PubMed] [Google Scholar]