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Gene Review

RT1-Da  -  RT1 class II, locus Da

Rattus norvegicus

Synonyms: DA1, H2-Ea, RT1-u
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Disease relevance of RT1-Da


High impact information on RT1-Da

  • Concanavalin A-activated spleen cells from acutely diabetic DP rats adoptively transfer diabetes only to recipients that express at least one RT1u haplotype [1].
  • Immune serum obtained from RT1u recipients that had rejected a RT1Aa disparate graft was able, when injected into cyclosporin-treated RT1u recipients, to restore their ability to reject a RT1Aa, but not a third-party RT1c, kidney [6].
  • Injection of RT1u rats with MRC OX8 mAb was highly effective at selectively depleting CD8+ cells from graft recipients but had no effect in prolonging the survival of RT1Aa disparate grafts despite the complete absence of CD8+ cells from the graft infiltrate, which included numerous CD4+ T cells and macrophages [6].
  • The testes of the RT1l animals showed an arrest of spermatogenesis at the early pachytene stage of the primary spermatocytes, and they were approximately 1/10 as heavy as the testes of the RT1l/u and RT1u/u animals [2].
  • We used intra-RT1 recombinant rat strains with recombinations between the RT1a and RT1u haplotypes on the disease permissive LEW non-MHC genome [7].

Chemical compound and disease context of RT1-Da


Biological context of RT1-Da

  • We have found entire sequence identity between five different inbred rat strains of the RT1u haplotype, which differs from previously published, incomplete sequences [10].
  • In a second experiment, rats from three strains that share the RT1u major histocompatibility complex haplotype of the BB/Wor and rats from three non-RT1u strains were lethally irradiated and reconstituted with DP BB/Wor bone marrow [11].
  • Humoral responses to non-inherited maternal class I antigens (class I NIMAs) were assessed in 3 groups of inbred rats expressing the RT1u phenotype [12].
  • In the fully major histocompatibility complex-disparate heart and skin transplantation models (LEW [RT1l]--> LEW.1W [RT1u]), a single dose of anti-RT7 mAb (10 mg/kg) was administered intravenously (day -1) [13].
  • To evaluate whether in vivo immunogenicity of MHC peptides is relevant to tolerance induction and to examine the effect of peptide specificity, we compared the effects on graft survival of well-defined, strain-specific immunogenic WF MHC class I peptides (RT1.AU) with closely related but non-strain-specific class I peptides derived from WAG (RT1U) [14].

Anatomical context of RT1-Da

  • Suppressor cells generated in cultures of WF (RT1u) with WRC stimulator cells potently suppressed a WF + WRCx test MLR, with less suppression when tested against either the WF + DAx or WF + BNx MLRs [15].
  • Recipients that are RT1u at only the class I A or C locus, but not at the class II B/D loci, do not develop diabetes after T cell transfer [1].
  • Genotypic mosaic rat livers were constructed by transplantation of carcinogen-altered F-344 (RT1Iv1) or WF (RT1u) donor liver cells into livers of WF X F-344 F1 host rats, whose liver cells bear alloantigens of both parental strains: WF and F-344, RT1u and RT1Iv1, respectively (J. M. Hunt et al., Cancer Res., 42: 227-236, 1982) [16].
  • In immunohistochemistry using haplotype-specific antibodies, lymphocytes showed RT1u class I expression as in the normal WAG thymus [17].
  • Streptozotocin-induced diabetic Lewis (RT1(1)) rats remained hyperglycemic (> 200 mg/dl) after intrahepatic preimmunization by injection of 200 low-temperature cultured (24 degrees C for 7 days) Wistar-Furth (WF, RT1u) rat islets into the portal vein with one injection (1 ml) of rat antilymphocyte serum intraperitoneally [18].

Associations of RT1-Da with chemical compounds

  • Grafts (RT1u/l) of different cellular composition were intraportally transplanted in streptozocin-induced diabetic rats (RT1n/n) [19].
  • Focusing on sex-difference in prolongation of allograft survival time, we have performed skin grafts between fully allogeneic rat strains, AO (RT1u) and DA (RT1a) with an immunosuppressant, cyclosporine [20].
  • In addition, Wistar Furth (RT1u) rat recipients of Buffalo (RT1b) heart allografts were treated with FTY720 alone or in combination with other agents [21].
  • Both AO (RT1u) and DZB (RT1u) rats were found to develop a membranous autoimmune glomerulopathy upon exposure to HgCl2 [22].
  • Fetal ventral mesencephalic tissue containing DA neuroblasts from Wistar-Furth (WF, RT1u) rat donors (9-12 mm CRL) were later implanted in striatum on the lesioned side [23].

Other interactions of RT1-Da

  • Here we describe the complementary DNA (cDNA) sequence encoding the alpha and beta chains of both the RT1-B and RT1-D locus genes of the rat RT1u haplotype [10].
  • Serological characterization of rat class II (RT1.B) alloantigens. Analysis of the RT1l, RT1u, and RT1n haplotypes [24].

Analytical, diagnostic and therapeutic context of RT1-Da

  • We utilized neonatal tolerance induction to prevent rejection of Wistar-Furth (WF) (RT1u) islet allografts by spontaneously diabetic BB recipients [25].
  • Purified islets from neonatal F-344 (RT1Lv1) rats were transplanted bilaterally under the kidney capsule of Wistar-Furth (W/F, RT1u) rats without immunosuppression [26].
  • Primary anti-MHC class I alloantibody responses, detected by indirect hemagglutination and complement-dependent cytotoxicity assays, were abrogated in high-responder WAG (RT1u) recipients of DA (RT1a) blood transfusions, given on days 0 and 7 of a 14-day course of rapamycin (3 mg/kg/day) [27].
  • Brown Norway (RT1n) to Lewis (RT1(1)) combination was used in the heart and pancreas transplantation models, whereas Buffalo (RT1b) to Wistar Furth (RT1u) was used in the kidney transplantation model [28].
  • Isografts of 1500 freshly isolated (n = 8) or 2500 frozen-thawed (n = 6) Wistar-Furth (RT1u/u) islets induced long-term normoglycemia after intrathymic transplantation (median survival time [MST] > 100 days in both groups), whereas isografts of 1500 frozen-thawed islets (n = 5) were inconsistent in restoring long-term normoglycemia [29].


  1. A major histocompatibility complex class II restriction for BioBreeding/Worcester diabetes-inducing T cells. Ellerman, K.E., Like, A.A. J. Exp. Med. (1995) [Pubmed]
  2. Growth and reproduction complex in the rat. Genes linked to the major histocompatibility complex that affect development. Kunz, H.W., Gill, T.J., Dixon, B.D., Taylor, F.H., Greiner, D.L. J. Exp. Med. (1980) [Pubmed]
  3. Non-major histocompatibility complex-linked diabetes susceptibility loci on chromosomes 4 and 13 in a backcross of the DP-BB/Wor rat to the WF rat. Martin, A.M., Blankenhorn, E.P., Maxson, M.N., Zhao, M., Leif, J., Mordes, J.P., Greiner, D.L. Diabetes (1999) [Pubmed]
  4. Mechanisms of indirect allorecognition: characterization of MHC class II allopeptide-specific T helper cell clones from animals undergoing acute allograft rejection. Waaga, A.M., Chandraker, A., Spadafora-Ferreira, M., Iyengar, A.R., Khoury, S.J., Carpenter, C.B., Sayegh, M.H. Transplantation (1998) [Pubmed]
  5. Association of spontaneous thyroiditis with the major histocompatibility complex of the rat. Colle, E., Guttmann, R.D., Seemayer, T.A. Endocrinology (1985) [Pubmed]
  6. T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity. Gracie, J.A., Bolton, E.M., Porteous, C., Bradley, J.A. J. Exp. Med. (1990) [Pubmed]
  7. MHC gene related effects on microglia and macrophages in experimental autoimmune encephalomyelitis determine the extent of axonal injury. Storch, M.K., Weissert, R., Steffer, A., Birnbacher, R., Wallström, E., Dahlman, I., Ostensson, C.G., Linington, C., Olsson, T., Lassmann, H. Brain Pathol. (2002) [Pubmed]
  8. Metabolic syndrome and aging in Wistar Ottawa Karlsburg W rats. van den Brandt, J., Kovacs, P., Klöting, I. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
  9. Development of follicular dendritic cells: a study using short-term bone marrow cell grafting in SCID mice. Yamakawa, M., Imai, Y., Dobashi, M., Kasajima, T. Histol. Histopathol. (1999) [Pubmed]
  10. Complementary DNA sequences encoding the rat MHC class II RT1-Bu and RT1-Du alpha and beta chains. Easterfield, A.J., Bradley, J.A., Bolton, E.M. Immunogenetics (2003) [Pubmed]
  11. Role of host immune system in BB/Wor rat. Predisposition to diabetes resides in bone marrow. Nakano, K., Mordes, J.P., Handler, E.S., Greiner, D.L., Rossini, A.A. Diabetes (1988) [Pubmed]
  12. Immune responses to noninherited maternal RT1A antigens in inbred rats. Propper, D.J., Woo, J., Stewart, K.N., Catto, G.R., Power, D.A. Transplantation (1991) [Pubmed]
  13. Long-term allograft acceptance induced by single dose anti-leukocyte common antigen (RT7) antibody in the rat. Ko, S., Jager, M.D., Tsui, T.Y., Deiwick, A., Dinkel, A., Rohde, F., Dahlke, M.H., Lauth, O., Wonigeit, K., Schlitt, H.J. Transplantation (2001) [Pubmed]
  14. Comparative studies of specific acquired systemic tolerance induced by intrathymic inoculation of a single synthetic Wistar-Furth (RT1U) allo-MHC class I (RT1.AU) peptide or WAG (RT1U)-derived class I peptide. Chowdhury, N.C., Saborio, D.V., Garrovillo, M., Chandraker, A., Magee, C.C., Waaga, A.M., Sayegh, M.H., Jin, M.X., Oluwole, S.F. Transplantation (1998) [Pubmed]
  15. Characterization of the Ia antigens involved in suppressor T cell generation in the rat. Uhteg, L.C., Salomon, D.R., Cohen, D.J., Cramer, D.V., Carpenter, C.B. Immunogenetics (1987) [Pubmed]
  16. Immunological approaches to the purification of putative premalignant hepatocytes from genotypic mosaic rat livers. Hunt, J.M., Buckley, M.T., Laishes, B.A., Dunsford, H.A. Cancer Res. (1985) [Pubmed]
  17. Implantation of cultured thymic fragments in congenitally athymic nude rats: ignorance of thymic epithelial haplotype in generation of alloreactivity. Schuurman, H.J., Vaessen, L.M., Vos, J.G., Hertogh, A., Geertzema, J.G., Brandt, C.J., Rozing, J. J. Immunol. (1986) [Pubmed]
  18. Induction of allogeneic islet survival by intrahepatic islet preimmunization and transient immunosuppression. Goss, J.A., Flye, M.W., Lacy, P.E. Diabetes (1996) [Pubmed]
  19. Transplantation of purified islet cells in diabetic rats. II. Immunogenicity of allografted islet beta-cells. Pipeleers, D.G., Pipeleers-Marichal, M., Vanbrabandt, B., Duys, S. Diabetes (1991) [Pubmed]
  20. Sex-associated differences in the survival of skin grafts in rats. Enhancement of cyclosporine immunosuppression in male compared with female recipients. Enosawa, S., Hirasawa, K. Transplantation (1989) [Pubmed]
  21. Immunosuppressive effects of FTY720 alone or in combination with cyclosporine and/or sirolimus. Wang, M.E., Tejpal, N., Qu, X., Yu, J., Okamoto, M., Stepkowski, S.M., Kahan, B.D. Transplantation (1998) [Pubmed]
  22. Susceptibility to the induction of either autoimmunity or immunosuppression by mercuric chloride is related to the major histocompatibility complex class II haplotype. Aten, J., Veninga, A., De Heer, E., Rozing, J., Nieuwenhuis, P., Hoedemaeker, P.J., Weening, J.J. Eur. J. Immunol. (1991) [Pubmed]
  23. Microglial cell responses to fetal ventral mesencephalic tissue grafting and to active and adoptive immunizations. Shinoda, M., Hudson, J.L., Strömberg, I., Hoffer, B.J., Moorhead, J.W., Olson, L. Exp. Neurol. (1996) [Pubmed]
  24. Serological characterization of rat class II (RT1.B) alloantigens. Analysis of the RT1l, RT1u, and RT1n haplotypes. Wettstein, P.J. Immunogenetics (1981) [Pubmed]
  25. Prevention of recurrent autoimmune diabetes in BB rats by anti-asialo-GM1 antibody. Jacobson, J.D., Markmann, J.F., Brayman, K.L., Barker, C.F., Naji, A. Diabetes (1988) [Pubmed]
  26. Initiation of rejection of established islet allografts by third-party thyroid allografts and splenic dendritic cells. Kover, K., Moore, W.V. Diabetes (1991) [Pubmed]
  27. The effects of rapamycin on humoral immunity in vivo. Suppression of primary responses but not of ongoing alloantibody synthesis or memory responses. Propper, D.J., Woo, J., Macleod, A.M., Catto, G.R., Thomson, A.W. Transplantation (1992) [Pubmed]
  28. Synergistic effects of mycophenolate mofetil and sirolimus in prevention of acute heart, pancreas, and kidney allograft rejection and in reversal of ongoing heart allograft rejection in the rat. Vu, M.D., Qi, S., Xu, D., Wu, J., Peng, J., Daloze, P., Sehgal, S., Leduc, B., Chen, H. Transplantation (1998) [Pubmed]
  29. Intrathymic transplantation of fresh and cryopreserved islets for the induction of a state of unresponsiveness in rats. Lakey, J.R., Warnock, G.L., Rajotte, R.V. Transplantation (1996) [Pubmed]
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