C A Janeway, B Broughton, L A Smith, T N Marion, K Bottomly
{"title":"Direct receptor:receptor interactions between T and B lymphocytes: idiotypic restriction in the antibody response to a cloned helper T cell receptor.","authors":"C A Janeway, B Broughton, L A Smith, T N Marion, K Bottomly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The concept of an immunological network includes the possibility of interactions between receptors on T and B lymphocytes, and such interactions, should they occur, might be expected to influence the repertoire of receptors in each set of cells. Indeed, B cell idiotype specific helper T cells, both MHC-restricted and MHC-unrestricted, have been reported and have been shown to influence the expression of the B cell repertoire. Likewise, it has been reported that B cells may influence the specificity of both regulatory and MHC-restricted T cells. However, interactions between receptors on cloned, MHC-restricted helper T cells and B cells have been difficult to document. Recently, we have taken advantage of an unusual cloned helper T cell line to demonstrate that anti-T cell receptor antibody is produced by direct receptor:receptor interactions between T and B lymphocytes, and that these interactions are not MHC restricted. However, these earlier studies did not address the question of whether such interactions led to activation of B cells expressing multiple distinct antibodies, or whether direct T cell receptor:B cell receptor interactions would lead to an idiotypically restricted B cell response. To address this question, we have now examined both monoclonal and polyclonal responses to the receptor of a conventional, MHC-restricted cloned T cell line, and have shown that these responses are of limited idiotype heterogeneity. Indeed, about 60% of antibodies produced to the receptor of this cloned line share idiotypic determinants, and appear to recognize a single epitope on the receptor. Idiotypically unrelated anti-receptor antibodies, although still specific for the cloned line, recognize what appears to be a distinct epitope on the receptor. These data suggest several conclusions. First, they demonstrate further that direct receptor:receptor interactions between helper T cells and B cells can occur, and can be mutually stimulatory for the two cell types. Second, as shown previously, such interactions are not MHC restricted. Third, such interactions can lead to an idiotypically restricted B cell response. Finally, it is interesting to compared these results with those of other investigators studying idiotype-specific helper T cells. As the cloned line used in this study is a conventional, MHC-restricted, antigen specific helper T cell bearing an alpha:beta heterodimeric receptor complex, and as its interaction with B cells is MHC unrestricted and leads to idiotypically restricted antibody responses, one might propose that such cells are candidates for a clone of an idiotype-specific helper.(ABSTRACT TRUNCATED AT 400 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 2","pages":"83-94"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H Miwa, H Konishi, N Kobayashi, K Kita, S Shirakawa, A Shimizu, T Honjo, M Hatanaka
{"title":"The T-cell receptor gene rearrangements in T-lineage tumors without OKT-3,4,6,8 markers.","authors":"H Miwa, H Konishi, N Kobayashi, K Kita, S Shirakawa, A Shimizu, T Honjo, M Hatanaka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the human system, discrete stages (I, II, and III) of intrathymic ontogeny have been defined on the basis of monoclonal antibody probes directed at unique T-lineage-specific surface glycoproteins. We have examined the relationship among T-cell receptor gene rearrangements and cell surface antigen expressions in T-cell malignancies. Twelve of 15 cases had the rearranged T-cell receptor beta chain gene, indicating that they represent cells already committed to the differentiated T-cell lineage at the gene level and are monoclonally proliferating regardless of the variable expression of surface antigens. We examined five cases of the earliest identifiable T-lineage cells (stage I) expressing WT-1 antigen without OKT-3, 4, 6, 8 antigens. Among them, two cases did not reveal the T-cell receptor beta chain gene rearrangements. In contrast, three cases demonstrated the T-cell receptor beta chain gene rearrangements even in stage I by the criteria of surface antigen expressions in contrast to the previous findings. Thus, we conclude that somatic rearrangement of the T-cell receptor gene of the beta chain occurs at the stage I level (early thymocyte) in the T-cell differentiation scheme. The phenotypically defined stage I T-cells consist of two populations with or without rearrangements of the T-cell receptor gene.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 1","pages":"37-42"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13993501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D Kabelitz, W R Herzog, K Heeg, H Wagner, J Reimann
{"title":"Human cytotoxic T lymphocytes. III. Large numbers of peripheral blood T cells clonally develop into allorestricted anti-viral cytotoxic T cell populations in vitro.","authors":"D Kabelitz, W R Herzog, K Heeg, H Wagner, J Reimann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cytotoxic T lymphocytes (CTL) recognize antigen in the context of syngeneic MHC class I gene products. The \"learning\" of MHC restriction is thought to take place during the early intrathymic development of cytotoxic lymphocyte precursors (CLP). This view does not allow for any significant number of \"allorestricted\" (as opposed to selfrestricted) T cells to occur among mature, peripheral T cells. Recent evidence indicates, however, that large numbers of antigen-specific, allorestricted CLP can be readily detected among splenic T cell populations from several strains of unprimed normal mice. The frequencies of allorestricted CLP as determined under limiting dilution (LD) culture conditions are in fact in the same order of magnitude as frequencies of selfrestricted CLP. These findings were at the origin of the present study, which was designed to investigate whether antigen-specific, allorestricted CTL populations could also be detected among human peripheral blood T lymphocytes. To address this issue we studied the CTL response to virus-infected allogeneic stimulator cells in two different LD systems. In the first system, peripheral T cells from normal donors were cocultured under precisely defined LD conditions with Epstein-Barr virus (EBV)-transformed allogeneic lymphoblastoid cell lines (LCL). Frequencies of CLP that lysed the stimulating LCL ranged from one in 70 to one in 200, while frequencies of CLP that lysed the respective allogeneic ConA blast targets were 3-40-fold lower. The split-well analysis suggested that a large fraction of developing CTL colonies specifically lysed the stimulating LCL targets but neither the respective ConA blasts nor HLA-mismatched third party LCL targets. CTL generated in this culture system thus displayed allorestricted specificity for LCL membrane antigens. Comparable results were obtained in a second LD system where T cells from normal donors were cocultured with mumps virus-infected allogeneic mononuclear cells (MNC) or ConA blasts. One of 600 to one of 2,800 T cells gave rise to a cytotoxic colony that lysed mumps virus-infected stimulator-derived ConA blast target cells. To assess the lytic specificity of the in vitro expanding CTL populations, individual microcultures were split into three aliquots and tested for cytolytic activity against mumps virus-infected and noninfected specific targets as well as mumps virus-infected, HLA-mismatched third party targets. Clonal CTL populations from four of seven donors lysed virus-infected stimulator targets but did not lyse either noninfected stimulator targets or mumps virus-infected third party targets, i.e., they again showed an antigen-specific allorestricted lytic r</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 1","pages":"49-60"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13993503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In situ hybridization with fluorochrome-labeled cloned DNA for quantitative determination of the homologous mRNA in individual cells.","authors":"K Pachmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The transcriptional activity of genes may provide a reliable parameter for the ability of cells to synthesize and express gene products. In order to detect such transcription products not only qualitatively but also quantitatively, a method was developed to fluorochrome label cloned DNA coding for part of the constant fragment of the immunoglobulin mu-chain. Microfluorimetry of the bound fluorochrome allows a quantitative estimation of the amount of cloned DNA in the DNA-mRNA hybrids formed in the cytoplasm of individual cells by in situ hybridization and thus a quantitative estimation of the respective mRNA content. Moreover, upon appropriate preparation of the cells the simultaneous quantitative detection of surface antigenic properties with antibodies labeled with a second fluorochrome is possible. Such a cell preparation procedure was optimized according to the highest signal obtainable. In the system chosen, exemplary cells from normal donors and different lymphoproliferative disorders were investigated for their ability to express the immunoglobulin mu-chain. Whereas a B-CLL was positive for the mu-mRNA and a T-CLL was negative for it as expected, a number of non-T non-B cALLs contained varying fractions of mu-mRNA positive cells with varying intensities. This method will allow a more exact definition of differentiative steps in B-cell development with respect to surface antigenic pattern, activation of the immunoglobulin genes, first of all the mu-gene, and immunoglobulin content and expression. The same method can also be applied to other gene sequences for which cloned DNA fragments or cDNA is available, and for which the transcriptional activity in cells of defined surface antigenic properties is to be determined.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 1","pages":"13-9"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Anti-mu antibody blocks LPS driven B cell differentiation by suppressing specific mRNAs.","authors":"R E Flahart, A R Lawton","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>High concentrations of anti-mu antibodies inhibit differentiation and increase proliferation of adult mouse splenic B cells stimulated by LPS. Cells from treated cultures express Ia antigens and on removal of anti-mu reexpress membrane IgM. They do not develop into plasmablasts secreting IgM. To investigate the mechanism of suppression we used Northern blots hybridized with cDNA probes to mu, kappa, J, and I-A beta chains to analyze RNAs in anti-mu suppressed and control cultures. Messenger RNAs for mu, kappa, and J chains but not I-A beta chain are diminished in anti-mu treated cells as compared to controls. Cells treated with anti-kappa antibodies have decreased mRNA levels for mu as well as kappa chains. Suppression mediated by modulation of the IgM receptor is not immunologically specific, but selectively inhibits expression of a cluster of unlinked genes which are coordinately activated during differentiation.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 2","pages":"61-8"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14281075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecules recognized by anti-idiotypic monoclonal antibodies to the B cell lymphoma, BCL1.","authors":"G S Tamura, M S McGrath, I L Weissman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Monoclonal and polyclonal antibodies to the variable portions of antigen receptors (anti-idiotypes and anti-idiotopes) are often employed to study the molecular nature and the biological role of these antigen receptors. Such antibodies are operationally defined as those antibodies which bind to a particular immunoglobulin but not to other immunoglobulins of the same class in a radioimmunoassay or ELISA. The monoclonal antibodies 32D1 and 31D1 were initially defined as anti-idiotypic as they recognized an immunoglobulin preparation from the murine B cell lymphoma BCL1, but not other immunoglobulins of the same isotype as assessed by a radioimmunoassay. A potential artifact in defining anti-idiotypic antibodies in this way is the possibility of copurification of antigen and antibody, resulting in the tentative identification of anti-antigen as anti-idiotype. Previous studies have demonstrated that BCL1-IgM is involved in binding of murine leukemia virus (MuLV), and BCL1 immunoglobulin and MuLV-gp70 apparently co-purified as an immune complex. Disruption of the immune complexes with SDS and sucrose gradient purification of the immunoglobulin was adequate to prepare BCL1 immunoglobulin free of gp70 as assessed by radioimmunoassay with the monoclonal anti-gp70 RA3-4A3. This preparation of immunoglobulin was used to show that 31D1 does not bind to BCL1 immunoglobulin, but to the contaminating gp70 in the BCL1 immunoglobulin preparation. However, MAb 32D1 was definitively proven to be anti-idiotypic as it recognized SDS sucrose density gradient purified IgM and immunoisolated heavy chain and light chain from BCL1 immunoglobulin. Several other lymphomas were recognized by mAb 32D1, including the T cell lymphoma UNC1 and the B cell lymphoma Balenlm17. To determine whether mAb 32D1 recognized immunospecific receptors on these lymphoma cell lines immunoprecipitation studies were performed. Immunoisolation and molecular analysis revealed that mAb 32D1 did not recognize the antigen receptor on these two cells, but instead recognized a cell-specific gp70. This observation demonstrates that monoclonal antibodies to known antigens (in this case an anti-idiotype) can crossreact with apparently unrelated molecules. The potential significance of this cross reaction to the antigens recognized by B cell lymphomas is discussed.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 4","pages":"243-53"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14633166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P K Mazzaferro, E A Repasky, J Black, R T Kubo, R B Bankert
{"title":"Biochemical and ultrastructural characterization of a novel cell structure associated with immunoglobulin secretion in B-lymphocytes.","authors":"P K Mazzaferro, E A Repasky, J Black, R T Kubo, R B Bankert","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the companion paper, it was established that a secretory form of immunoglobulin, sIg, is present at or near the cell surface. This unexpected occurrence of sIg was postulated to be due to the labelling of sIg which remains temporarily associated with the cell packaged in a vesicle which appears to bud from the plasma membrane at a single pole of the cell. The question that is addressed in this report is whether or not this polar accumulation of sIg represents a common pathway for the exit of this protein which is used by antibody-producing cells. This question is important since, in spite of the fact that the intracellular events associated with immunoglobulin synthesis (processing and movement between subcellular compartments) have been defined, very little data exists on how or where immunoglobulin finally leaves the plasma cell. This question was approached here by first demonstrating that the polar immunoglobulin secretory vesicles (ISV) are associated with several sIg-producing cells including other hybridomas, B-cell lines, and mitogen-activated spleen cells. The second approach was to characterize the ISV on the cell ultrastructurally and to establish that these vesicles are released from the cell carrying with them sIg. Isolated vesicles released from biosynthetically labeled Ig-producing cells were analyzed by SDS-PAGE in order to confirm the presence of sIg and to determine the number of other proteins associated with the ISV, their molecular weights, and the degree of disulfide crosslinking of the molecules comprising this structure. Finally, the kinetics of sIg release was established by a pulse chase protocol for biosynthetically labeled cells, and by monitoring the release of radioactive Ig from surface iodinated cells. As was predicted from our biochemical studies of the ISV, we observed a very slow phase of sIg release as well as a rapid release phase. Our studies have established that at least one of the pathways for the release of Ig from hybridomas, B-cell lines, and normal splenic B-cells is via a polar multivesiculated structure that we have termed ISV, and that the sIg can be released either as a free form of the protein or packaged within a satellite vesicle which may release the sIg later and perhaps at considerable distance from the cell that produced it.</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 5","pages":"293-306"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14633169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An essential role for interleukin 1 and a dual function for interleukin 2 in the immune response of murine B lymphocytes to sheep erythrocytes.","authors":"M K Hoffmann, K M Gilbert, J A Hirst, M Scheid","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The macrophage-derived lymphokine interleukin 1 (IL-1) and the T cell-derived lymphokine interleukin 2 (IL-2) help B lymphocytes to generate antibodies against sheep erythrocytes in vitro. It has been difficult to determine whether these factors act on antigen-reactive B cells directly or via accessory cells, since it is not technically feasible to prepare completely homogenous cell populations. Therefore we examined the question of lymphokine action on B cells using an indirect approach. First we determined effects of the two factors in the phenotypic differentiation assay, a short-term culture of cloned B cells certainly free of accessory cells. Next, we investigated whether the effects seen in this assay could be related to results obtained in the long-term (four-day) assay of antibody production. Interleukin 1 induced cloned 70Z/3 B lymphocytes to express new cell surface markers in the phenotypic B cell differentiation assay. IL-2 rendered these B cells refractory to differentiation caused by IL-1. In the antibody production assay, IL-1 controlled, as was shown previously, an early phase of the response in which B cells become responsive to T cell-derived helper factors. In order to demonstrate the requirement for IL-1, it was necessary to rigorously prevent endogenous IL-1 production. Synergy between IL-1 and IL-2 was observed when IL-2 was given as late as day 2 of a four-day culture period. This synergy was seen over a broad dose range of IL-2 (10-1,000 U/ml). However, IL-2, when added in high concentrations (200-1,000 U/ml) during the early (IL-1-dependent) phase of the B cell response inhibited antibody production.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 1","pages":"29-36"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14634020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C Martinez, A Coutinho, A Bandeira, A de la Hera, M Toribio, M A Marcos, P Pereira
{"title":"Sporadic idiotypic cross-reactivities between antibodies and T helper cells: one example of aleatory expression of T cell idiotypes.","authors":"C Martinez, A Coutinho, A Bandeira, A de la Hera, M Toribio, M A Marcos, P Pereira","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Idiotypic cross-reactivities between T and B cell receptors have been taken in the past to suggest VH-gene expression by both types of lymphocytes. More recently, after the molecular characterization of TcR, those observations were reinterpreted to indicate idiotypic network regulation, operating to select cross-reactive idiotypes in both B and T cell compartments. In support of these views, it has been shown that T cell expression of idiotypes is controlled by IgH-linked genes and markedly altered in B cell-deprived mice, and that T cells \"learn\" idiotype expression from the B cell compartment in the first few weeks of life. In most of these studies, aleatory idiotype cross-reactivities have not been sufficiently considered. Given the large diversity of antibodies and TcR, and the degeneracy of antibody-ligand interactions, it could be expected that a (monoclonal) anti-idiotypic reagent prepared against an antibody idiotope will always \"cross-react\" with some TcR variable regions. If these will be \"major\" T cell clonotypes, situations of idiotype sharing by B and T cells can be found which indicate neither VH-gene expression by T cells nor idiotypic network regulation. We report here one example of such aleatory expression of antibody idiotypes by T lymphocytes. A monoclonal anti-idiotypic antibody directed to anti-TNP antibodies of BALB/c mice specifically inhibits the growth and effector activity of C57BL/6 anti-NP-self helper T cells, while failing to interact with either BALB/c anti-NP-self or C57BL/6 anti-TNP-self helper cells. The clonotypic nature of these interactions could also be demonstrated by the specific induction of IL-2 production in the appropriate helper T cells by the anti-idiotypic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 1","pages":"21-8"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14111811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of suppressor T cells in the expression of immune response gene function.","authors":"P E Jensen, J A Kapp, C W Pierce","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mechanisms underlying major histocompatibility complex (MHC)-linked immune response (Ir) gene regulation of immune responses have been the subject of considerable interest and debate in recent years. Two general mechanisms have been proposed to account for antigen-specific, Ir gene-mediated unresponsiveness. In one, defective antigen presentation resulted from the failure of processed nominal antigen and Ia antigen to associate on the antigen presenting cell membrane in a manner sufficient for helper T cell (Th cell) activation. By contrast, it has been proposed that selected Th cell clones were deleted from the repertoire during ontogeny or otherwise rendered unresponsive to the antigen-Ia complex, i.e., functionally deleted. Either of these mechanisms would account for the deficient activation of antigen-specific, Th cells observed in genetic low or nonresponder mice. In addition, the failure of mice to respond to certain antigens under Ir gene control has been attributed to the activation of specific suppressor T (Ts) cells. The latter mechanism might be considered a corollary or subset of the clonal deletion model. However, an important distinction exists. In the case of active, Ts cell-mediated Ir gene regulation, genetic low responder animals should retain the capacity for antigen-induced activation of Th cells, or Th cell activity should be demonstrable in these mice. In this communication, experiments are described which are designed to evaluate the possibility that active Ts cell-mediated regulatory mechanisms were of general importance in mediating Ir gene-related unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77639,"journal":{"name":"The Journal of molecular and cellular immunology : JMCI","volume":"3 5","pages":"267-75"},"PeriodicalIF":0.0,"publicationDate":"1987-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14113582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}