The Functional Link Between the Immune Suppression Gene and Mhc Class II Molecules

Overview

Journal Immunogenetics

Specialties Allergy & Immunology
Genetics

Date 1988 Jan 1

PMID 2453460

Citations 1

Authors

K Mizuno

S Tsuchimoto

Y Matsuno

T Niiyama

H Fujii

T Natori

M Aizawa

Affiliations

Soon will be listed here.

Abstract

The immune response to bovine insulin (BI) in the rat is controlled by the major histocompatibility complex (Mhc)-linked immune response gene (Ir-BI) and immune suppression gene (Is-BI). In the present study, we investigated the low responsiveness to BI in the WKAH rat (RT1k) and attempted to explore the functional link between Is-BI and Mhc class II molecules. Lymph node cells (LNC) from the low responder (WKAH) rats responded well to BI when a large amount of antigen was added to the culture in vitro or after OX8-bearing (OX8+) T cells were eliminated. These LNC, after the elimination of OX8+ cells, could show the RT1.Dk-restricted proliferative response upon in vitro challenge with BI, BI-B chain, or pork insulin. In addition, OX8+ T cells, which were activated with BI and antigen-presenting cells (APC) in vitro, suppressed the anti-BI response of W3/25-bearing proliferating T cells from BI-immunized rats. The results have demonstrated that proliferating T-cell repertoires do exist to BI, which recognize BI-B chain in the context of RT1.Dk molecules in the WKAH rat, and that the state of low responsiveness is mediated to a great extent by antigen-specific OX8+ suppressor T (Ts) cells. Furthermore, the elimination of APC or the addition to RT1.Bk-specific monoclonal antibody in the in vitro secondary activation culture of Ts cells diminished the suppressive activity of OX8+ Ts cells. In the induction phase of Ts cells it therefore seems to be necessary for these cells to recognize BI together with RT1.Bk molecules on APC.

Citing Articles

Regulatory role of OX22high T cells in mercury-induced autoimmunity in the brown Norway rat.

Mathieson P, Thiru S, Oliveira D J Exp Med. 1993; 177(5):1309-16.

PMID: 8478610 PMC: 2191016. DOI: 10.1084/jem.177.5.1309.

References

Dessi V, Sercarz E . Selective reversal of H-2-linked genetic unresponsiveness to lysozymes. II. Alteration in the T helper/T suppressor balance, owing to gene(s) linked to Ir-2, leads to responsiveness in BALB.B. Eur J Immunol. 1986; 16(5):486-92. DOI: 10.1002/eji.1830160504. View

Yowell R, Araneo B, Miller A, Sercarz E . Amputation of a suppressor determinant on lysozyme reveals underlying T-cell reactivity to other determinants. Nature. 1979; 279(5708):70-1. DOI: 10.1038/279070a0. View

Debre P, Kapp J, Dorf M, 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; 142(6):1447-54. PMC: 2190080. DOI: 10.1084/jem.142.6.1447. View

Tada T, Taniguchi M, David C . Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex. J Exp Med. 1976; 144(3):713-25. PMC: 2190403. DOI: 10.1084/jem.144.3.713. View

Dorf M, Benacerraf B . Suppressor cells and immunoregulation. Annu Rev Immunol. 1984; 2:127-57. DOI: 10.1146/annurev.iy.02.040184.001015. View

Ikezawa Z, Arden B, Nagy Z, Klein J . Feedback regulation of immune suppression by a suppressor factor. Eur J Immunol. 1984; 14(8):681-6. DOI: 10.1002/eji.1830140802. View

Schwartz R, David C, Dorf M, Benacerraf B, Paul W . Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion. Proc Natl Acad Sci U S A. 1978; 75(5):2387-91. PMC: 392558. DOI: 10.1073/pnas.75.5.2387. View

Baxevanis C, Ishii N, Nagy Z, Klein J . H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway. J Exp Med. 1982; 156(3):822-33. PMC: 2186798. DOI: 10.1084/jem.156.3.822. View

Elder M, Maclaren N, Riley W, McConnell T . Gastric parietal cell and other autoantibodies in the BB rat. Diabetes. 1982; 31(4 Pt 1):313-8. DOI: 10.2337/diab.31.4.313. View

10.

Kapp J, Pierce C, SCHLOSSMAN S, Benacerraf B . Genetic control of immune responses in vitro. V. Stimulation of suppressor T cells in nonresponder mice by the terpolymer L-glutamic acid 60-L-alanine 30-L-tyrosine 10 (GAT). J Exp Med. 1974; 140(3):648-59. PMC: 2139614. DOI: 10.1084/jem.140.3.648. View

11.

Benacerraf B, Germain R . The immune response genes of the major histocompatibility complex. Immunol Rev. 1978; 38:70-119. DOI: 10.1111/j.1600-065x.1978.tb00385.x. View

12.

Woda B, LIKE A, Padden C, McFadden M . Deficiency of phenotypic cytotoxic-suppressor T lymphocytes in the BB/W rat. J Immunol. 1986; 136(3):856-9. View

13.

LIKE A, Appel M, Rossini A . Autoantibodies in the BB/W rat. Diabetes. 1982; 31(9):816-20. DOI: 10.2337/diab.31.9.816. View

14.

Schwartz R . A clonal deletion model for Ir gene control of the immune response. Scand J Immunol. 1978; 7(1):3-10. DOI: 10.1111/j.1365-3083.1978.tb00420.x. View

15.

GERSHON R, Kondo K . Infectious immunological tolerance. Immunology. 1971; 21(6):903-14. PMC: 1408252. View

16.

Natori T, Fujimoto Y, Ikeda H, Ishikawa N, Ishikura H, Matsuno Y . The RT1.B/D-region products defined by rat monoclonal alloantibodies. Immunogenetics. 1985; 22(5):511-6. DOI: 10.1007/BF00418096. View

17.

Ikezawa Z, Walden P, Arden B, Nagy Z, Klein J . Composition of a suppressor factor that inhibits the immune response to lactate dehydrogenase B. Scand J Immunol. 1984; 20(2):113-23. DOI: 10.1111/j.1365-3083.1984.tb00984.x. View

18.

Jandinski J, Li J, Wettstein P, Frelinger J, Scott D . Role of self carriers in the immune response and tolerance. V. Reversal of trinitrophenyl-modified self suppression of the B-cell response by blocking of H-2 antigens. J Exp Med. 1980; 151(1):133-43. PMC: 2185759. DOI: 10.1084/jem.151.1.133. View

19.

Epstein R, Cohn M . T-cell inhibition of humoral responsiveness. I. Experimental evidence for restriction by the K- and/or D-end of the H-2 gene complex. Cell Immunol. 1978; 39(1):110-24. DOI: 10.1016/0008-8749(78)90088-6. View

20.

Bevan M, Fink P . The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978; 42:3-19. DOI: 10.1111/j.1600-065x.1978.tb00256.x. View