Abstract
Antigen-specific suppression to poly(Glu50-Tyr50) (GT) is under the control of two complementary immune suppressor (Is) genes located in the major histocompatibility (H-2) complex of the mouse. Suppressor strains of mice produce both suppressor T (Ts) cells and Ts-derived suppressor factors (TsF) that bear antigenic determinants of the I-J subregion of the H-2 complex. Nonsuppressor strains of mice, on the other hand, are not suppressed by GT preimmunization. These nonsuppressor mice, however, can be classified according to those that lack the ability to make GT-specific T cell-derived suppressor factor (GT-TsF) after GT injection (i.e., H-2a, I-Jk mice) and those that lack the ability to be suppressed by the appropriate GT-TsF (i.e., H-2b,g2, I-Jb mice). In the present study, we demonstrate that (H-2a x H- 2b,g2)F1 hybrid mice produce distinct GT-specific suppressor factors of both parental I-J haplotypes. Moreover, only the I-Jb-bearing GT-TsF derived from these F1 hybrid mice is able to induce second-order suppressor cells (Ts2). This is consistent with the observation that injection of GT-TsF1 derived from C57BL/6 (I-Jb) mice into A/J (I-Jk) mice leads to the production of an antigen-specific I-Jk GT-TsF2. Our results suggest that Is gene complementation occurs through a different cellular mechanism that was previously observed for Ir gene complementation. Further, we show that complementing (non-suppressor X nonsuppressor)F1 hybrid mice produce an I-Jb (and not an I-Jk) GT-TsF1 and an I-Jk (not an I-Jb) GT-TsF2, thus suggesting a heterogeneity of Ia loci within the I-J subregion. Data presented in the present study suggest that there may be even more heterogeneity within the I-J subregion than has has been heretofore reported with regard to I-J expression on Ts.
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Selected References
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- Benacerraf B., Dorf M. E. Genetic control of specific immune responses and immune suppressions by I-region genes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):465–475. doi: 10.1101/sqb.1977.041.01.054. [DOI] [PubMed] [Google Scholar]
- Benacerraf B., Germain R. N. The immune response genes of the major histocompatibility complex. Immunol Rev. 1978;38:70–119. doi: 10.1111/j.1600-065x.1978.tb00385.x. [DOI] [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]
- Debré P., Waltenbaugh C., Dorf M., Benacerraf B. Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid50-L-tyrosine50 (GT). J Exp Med. 1976 Jul 1;144(1):272–276. doi: 10.1084/jem.144.1.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorf M. E., Benacerraf B. Complementation of H-2-linked Ir genes in the mouse. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3671–3675. doi: 10.1073/pnas.72.9.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Germain R. N., Theze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Antigen-specific T cell-mediated suppression. II. In vitro induction by I-J-coded L-glutamic acid50-L-tyrosine50 (GT)-specific T cell suppressor factor (GT-T8F) of suppressor T cells (T82) bearing distinct I-J determinants. J Immunol. 1978 Aug;121(2):602–607. [PubMed] [Google Scholar]
- Germain R. N., Waltenbaugh C., Benacerraf B. Antigen-specific T cell-mediated suppression. V. H-2-linked genetic control of distinct antigen-specific defects in the production and activity of L-glutamic acid50-L-tyrosine50 suppressor factor. J Exp Med. 1980 May 1;151(5):1245–1259. doi: 10.1084/jem.151.5.1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greene M. I., Dorf M. E., Pierres M., Benacerraf B. Reduction of syngeneic tumor growth by an anti-I-J-alloantiserum. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5118–5121. doi: 10.1073/pnas.74.11.5118. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ju S. T., Benacerraf B., Dorf M. E. Idiotypic analysis of antibodies to poly(Glu60Ala30Tyr10): interstrain and interspecies idiotypic crossreactions. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6192–6196. doi: 10.1073/pnas.75.12.6192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ju S. T., Cramer D. V., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. V. Distribution of an interspecies cross-reactive idiotype. J Immunol. 1979 Aug;123(2):877–883. [PubMed] [Google Scholar]
- Mishell R. I., Dutton R. W. Immunization of dissociated spleen cell cultures from normal mice. J Exp Med. 1967 Sep 1;126(3):423–442. doi: 10.1084/jem.126.3.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murphy D. B., Yamauchi K., Habu S., Eardley D. D., Gershon R. K. T cells in a suppressor circuit and non-T:non-B cells bear different I-J determinants. Immunogenetics. 1981;13(3):205–213. doi: 10.1007/BF00350787. [DOI] [PubMed] [Google Scholar]
- Okuda K., Minami M., Sherr D. H., Dorf M. E. Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XI. Pseudogenetic restrictions of hybridoma suppressor factors. J Exp Med. 1981 Aug 1;154(2):468–479. doi: 10.1084/jem.154.2.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierres M., Germain R. N., Dorf M. E., Benacerraf B. In vivo effects of anti-Ia alloantisera. I. Elimination of specific suppression by in vivo administration of antisera specific for I-J controlled determinants. J Exp Med. 1978 Mar 1;147(3):656–666. doi: 10.1084/jem.147.3.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H., Dorf M. E., Benacerraf B., Paul W. E. The requirement for two complementing Ir-GLphi immune response genes in the T-lymphocyte proliferative response to poly-(Glu53Lys36Phe11). J Exp Med. 1976 Apr 1;143(4):897–905. doi: 10.1084/jem.143.4.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz R. H., Yano A., Stimpfling J. H., Paul W. E. Gene complementation in the T-lymphocyte proliferative response to poly (Glu55Lys36Phe9)n. A demonstration that both immune response gene products must be expressed in the same antigen-presenting cell. J Exp Med. 1979 Jan 1;149(1):40–57. doi: 10.1084/jem.149.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seman M., Zilberfarb V. Complementation between a gene of the I-E subregion and a non-H-2 gene in the class-specific suppression of IgG2a antibody to sheep erythrocytes. Immunogenetics. 1981;12(1-2):89–99. doi: 10.1007/BF01561653. [DOI] [PubMed] [Google Scholar]
- Sy M. S., Nisonoff A., Germain R. N., Benacerraf B., Greene M. I. Antigen- and receptor-driven regulatory mechanisms. VIII. Suppression of idiotype-negative, p-azobenzenearsonate-specific T cells results from the interaction of an anti-idiotypic second-order T suppressor cell with a cross-reactive-idiotype-positive, p-azobenzenearsonate-primed T cell target. J Exp Med. 1981 Jun 1;153(6):1415–1425. doi: 10.1084/jem.153.6.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada T., Takemori T., Okumura K., Nonaka M., Tokuhisa T. Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells. J Exp Med. 1978 Feb 1;147(2):446–458. doi: 10.1084/jem.147.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thèze J., Waltenbaugh C., Dorf M. E., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT) II. Presence of I-J determinants on the GT-suppressive factor. J Exp Med. 1977 Jul 1;146(1):287–292. doi: 10.1084/jem.146.1.287. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waltenbaugh C., Debré P., Thèze J., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). I. Production, characterization, and lack of H-2 restriction for activity in recipient strain. J Immunol. 1977 Jun;118(6):2073–2077. [PubMed] [Google Scholar]
- Waltenbaugh C., Dessein A., Benacerraf B. Characterization of the primary IgM response to GAT and GT: conditions required for the detection of IgM antibodies. J Immunol. 1979 Jan;122(1):27–33. [PubMed] [Google Scholar]
- Waltenbaugh C. Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies. J Exp Med. 1981 Nov 1;154(5):1570–1583. doi: 10.1084/jem.154.5.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Waltenbaugh C., Thèze J., Kapp J. A., Benacerraf B. Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). III. Generation of suppressor T cells by a suppressive extract derived from GT-primed lymphoid cells. J Exp Med. 1977 Oct 1;146(4):970–985. doi: 10.1084/jem.146.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
