Abstract
The locus of the gene that codes for the antigen-specific suppressive T- cell factor was determined to be in a new subregion "I-J" which locates between I-B and I-C subregions in the H-2 histocompatibility complex. This was shown by two different lines of evidence: (a) The absorbing capacity for the suppressive T-cell factor of several alloantisera against restricted I subregions did not correlate with their specificity for previously known Ia molecules which are coded for by genes in I-A and I-C subregions, but was associated with the specificity for the products of genes putatively present between I-B and I-C subregions. By the occurrence of special recombinant strains, i.e. B10.A(5R), B10.A(3R), B10.S(9R), and B10.HTT, which differ with respect to the I-J subregion, we were able to produce alloantisera which distinguish I-J subregion gene products. The absorption studies using these special alloantisera directed to I-J subregion clearly indicated that the suppressive T-cell factor is a product of I-J subregion gene(s), and that the molecule is distinct from known Ia molecules expressed on splenic B cells. (b) Taking advantage of the fact that there is a strict histocompatibility requirement for the effective suppression between the donor and recipient strains of the suppressive T-cell factor, we were able to determine the required identities of the genes in the H-2 complex existing among those present between I-B and I-C. Again, utilizing the T-cell factors obtained from special recombinant strains, i.e. B10.A(4R) and B10.A(5R), we were able to locate the gene that codes for the suppressive T-cell factor reactive only with relevant haplotype strains between I-B and I-C subregions. These results are most reasonably explained by the presence of a new subregion I-J which is specialized in coding for the suppressive T-cell factor as a different molecule from previously known Ia molecules.
Full Text
The Full Text of this article is available as a PDF (973.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Armerding D., Sachs D. H., Katz D. H. Activation of T and B lymphocytes in vitro. III. Presence of Ia determinants on allogeneic effect factor. J Exp Med. 1974 Dec 1;140(6):1717–1722. doi: 10.1084/jem.140.6.1717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullen S. E., David C. S., Cone J. L., Sachs D. H. Evidence for more than one Ia antigenic specificity on molecules determined by the I-A subregion of the mouse major histocompatibility complex. J Immunol. 1976 Feb;116(2):549–553. [PubMed] [Google Scholar]
- David C. S., Shreffler D. C., Frelinger J. A. New lymphocyte antigen system (Lna) controlled by the Ir region of the mouse H-2 complex. Proc Natl Acad Sci U S A. 1973 Sep;70(9):2509–2514. doi: 10.1073/pnas.70.9.2509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debré P., Kapp J. A., Benacerraf B. Genetic control of specific immune suppression. I. Experimental conditions for the stimulation of suppressor cells by the copolymer L-glutamic acid50-L-tyrosine50 (GT) in nonresponder BALB/c mice. J Exp Med. 1975 Dec 1;142(6):1436–1446. doi: 10.1084/jem.142.6.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Debré P., Kapp J. A., Dorf M. E., Benacerraf B. Genetic control of specific immune suppression. II. H-2-linked dominant genetic control of immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). J Exp Med. 1975 Dec 1;142(6):1447–1454. doi: 10.1084/jem.142.6.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Götze D., Reisfeld R. A., Klein J. Serologic evidence for antigens controlled by the Ir region in mice. J Exp Med. 1973 Oct 1;138(4):1003–1008. doi: 10.1084/jem.138.4.1003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapp J. A., Pierce C. W., De la Croix F., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). J Immunol. 1976 Feb;116(2):305–309. [PubMed] [Google Scholar]
- Katz D. H., Graves M., Dorf M. E., Dimuzio H., Benacerraf B. Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J Exp Med. 1975 Jan 1;141(1):263–268. doi: 10.1084/jem.141.1.263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Munro A. J., Taussig M. J., Campbell R., Williams H., Lawson Y. Antigen-specific T-cell factor in cell cooperation: physical properties and mapping in the left-hand (K) half of H-2. J Exp Med. 1974 Dec 1;140(6):1579–1587. doi: 10.1084/jem.140.6.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy D. B., Herzenberg L. A., Okumura K., Herzenberg L. A., McDevitt H. O. A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):699–712. doi: 10.1084/jem.144.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okumura K., Herzenberg L. A., Murphy D. B., McDevitt H. O., Herzenberg L. A. Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes. J Exp Med. 1976 Sep 1;144(3):685–698. doi: 10.1084/jem.144.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sachs D. H., Cone J. L. A mouse B-cell alloantigen determined by gene(s) linked to the major histocompatibility complex. J Exp Med. 1973 Dec 1;138(6):1289–1304. doi: 10.1084/jem.138.6.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shreffler D. C., David C. S. The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization. Adv Immunol. 1975;20:125–195. doi: 10.1016/s0065-2776(08)60208-4. [DOI] [PubMed] [Google Scholar]
- Tada T., Taniguchi M., Takemori T. Properties of primed suppressor T cells and their products. Transplant Rev. 1975;26:106–129. doi: 10.1111/j.1600-065x.1975.tb00177.x. [DOI] [PubMed] [Google Scholar]
- Takemori T., Tada T. Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization. J Exp Med. 1975 Nov 1;142(5):1241–1253. doi: 10.1084/jem.142.5.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taniguchi M., Hayakawa K., Tada T. Properties of antigen-specific suppressive T cell factor in the regulation of antibody response of the mouse. II. In vitro activity and evidence for the I region gene product. J Immunol. 1976 Feb;116(2):542–548. [PubMed] [Google Scholar]
- Taniguchi M., Tada T., Tokuhisa T. Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. III. Dual gene control of the T-cell-mediated suppression of the antibody response. J Exp Med. 1976 Jul 1;144(1):20–31. doi: 10.1084/jem.144.1.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Taussig M. J., Munro A. J., Campbell R., David C. S., Staines N. A. Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers. J Exp Med. 1975 Sep 1;142(3):694–700. doi: 10.1084/jem.142.3.694. [DOI] [PMC free article] [PubMed] [Google Scholar]
