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1.
Front Immunol ; 11: 82, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117244

RESUMO

B-1a cells produce "natural" antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation. Compared to FCRL6- pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6+ progenitors, yielded VH repertoires with biased distal Ighv segment accessibility, constrained diversity, and hydrophobic and charged CDR-H3 sequences. Beyond nascent autoreactivity, VH11 productivity, which predominates phosphatidylcholine-specific B-1a B cell receptors (BCRs), was higher for FCRL6+ cells as was pre-BCR formation, which was required for Myc induction and VH11, but not VH12, B-1a development. Thus, FCRL6 revealed unexpected heterogeneity in the developmental origins, regulation, and selection of natural Abs at the pre-BCR checkpoint with implications for autoimmunity and lymphoproliferative disorders.

3.
Front Immunol ; 10: 945, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130948

RESUMO

It is now evident from studies of mice unable to secrete IgM that both non-immune "natural" and antigen-induced "immune" IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since identification of its Fc receptor (FcµR) by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. Unlike Fc receptors for switched Ig isotypes (e.g., FcγRs, FcεRs, FcαR, Fcα/µR, pIgR, FcRn), FcµR is selectively expressed by lymphocytes: B, T, and NK cells in humans and only B cells in mice. FcµR may have dual signaling ability: one through a potential as yet unidentified adaptor protein non-covalently associating with the FcµR ligand-binding chain via a His in transmembrane segment and the other through its own Tyr and Ser residues in the cytoplasmic tail. FcµR binds pentameric and hexameric IgM with a high avidity of ~10 nM in solution, but more efficiently binds IgM when it is attached to a membrane component via its Fab region on the same cell surface (cis engagement). Four different laboratories have generated Fcmr-ablated mice and eight different groups of investigators have examined the resultant phenotypes. There have been some clear discrepancies reported that appear to be due to factors including differences in the exons of Fcmr that were targeted to generate the knockouts. One common feature among these different mutant mice, however, is their propensity to produce autoantibodies of both IgM and IgG isotypes. In this review, we briefly describe recent findings concerning the functions of FcµR in both mice and humans and propose a model for how FcµR plays a regulatory role in B cell tolerance.

4.
Curr Top Microbiol Immunol ; 408: 25-45, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28702710

RESUMO

Since the bona fide Fc receptor for IgM antibody (FcµR) was identified eight years ago, much progress has been made in defining its biochemical nature, cellular distribution, and effector function. However, there are clearly conflicting results, especially about the cellular distribution and function of murine FcµR. In this short article, we will discuss recent findings from us and other investigators along with our interpretations and comments that may help to resolve the existing puzzles and should open new avenues of investigation.


Assuntos
Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Receptores Fc/imunologia , Receptores Fc/metabolismo , Animais
5.
J Immunol ; 194(4): 1975-82, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25601920

RESUMO

The IgM Fc receptor (FcµR) is the newest FcR, and coligation of FcµR and Fas/CD95 on Jurkat cells with agonistic IgM anti-Fas mAb was shown to inhibit Fas-induced apoptosis. The ligand-binding activity of human FcµR was further examined. FcµR-mediated protection from apoptosis was partially blocked by addition of 10(4) molar excess of IgM or its soluble immune complexes, but it could be inhibited by addition of 10-fold excess of IgM anti-CD2 mAb. This suggests that FcµR binds more efficiently to the Fc portion of IgM reactive with plasma-membrane proteins than to the Fc portion of IgM in solution. The former interaction occurred in cis on the same cell surface, but not in trans between neighboring cells. This cis engagement of FcµR resulted in modulation of Ca(2+) mobilization via CD2 on Jurkat cells or BCRs on blood B cells upon cross-linkage with the corresponding IgM mAbs. Several functional changes were observed with FcµR mutants: 1) significant increase in IgM ligand binding in the cytoplasmic tail-deletion mutant, 2) enhanced cap formation in FcµR upon IgM binding at 4°C with a point mutation of the transmembrane His to Phe, and 3) less protective activity of FcµR in IgM anti-Fas mAb-mediated apoptosis assays with a point mutation of the membrane-proximal Tyr to Phe. These findings show the importance of the cis engagement of FcµR and its critical role in receptor function. Hence, FcµR on B, T, and NK cells may modulate the function of surface proteins recognized by natural or immune IgM Abs on the shared membrane cell surface.


Assuntos
Fragmentos Fc das Imunoglobulinas/imunologia , Ativação Linfocitária/imunologia , Receptores Fc/imunologia , Transdução de Sinais/imunologia , Animais , Complexo Antígeno-Anticorpo/imunologia , Apoptose/imunologia , Linfócitos B/imunologia , Linhagem Celular , Imunofluorescência , Humanos , Células Jurkat , Células Matadoras Naturais/imunologia , Ligantes , Camundongos , Mutagênese Sítio-Dirigida
6.
Monoclon Antib Immunodiagn Immunother ; 33(6): 393-400, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25545208

RESUMO

A panel of six different murine hybridoma clones secreting IgG monoclonal antibodies (MAbs) specific for the human IgM Fc receptor (FcµR) was generated. All MAbs specifically precipitated a major protein of ∼60 kDa from membrane lysates of FcµR-bearing, but not FcµR-negative, cells as did IgM-ligands. Pre-incubation of membrane lysate of FcµR-bearing cells with these MAbs completely removed the ∼60 kDa IgM-reactive protein. By using recombinant human/mouse chimeric FcµR proteins, the epitope recognized by HM7 and HM10 MAbs was mapped to the Ig-like domain of human FcµR, whereas the other MAbs recognized the stalk region. Pre-incubation of FcµR(+) cells with the Ig-like domain-specific MAbs, but not with others, markedly inhibited subsequent IgM-ligand binding. A similar, but much weaker, inhibition was also observed when the incubation order was reversed. When FcµR(+) cells were simultaneously incubated with both IgM-ligands and MAbs, HM7 MAb efficiently competed with IgM for FcµR binding. Unlike control Jurkat cells, FcµR-bearing cells were resistant to apoptosis induced by agonistic IgM anti-Fas MAb (CH11); however, addition of the HM7 MAb inhibited the interaction of the Fc portion of CH11 MAb with FcµR, thereby promoting apoptosis of FcµR-bearing Jurkat cells. The variable regions of the HM7 MAb were composed of Ighv14-3, Ighd1-2, and Ighj2 for the γ2b heavy chain and Igk3-4 and Igkj2 for the κ light chain. These findings suggest that HM7 MAb efficiently blocks the ligand-binding activity of FcµR.


Assuntos
Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Hibridomas/metabolismo , Receptores Fc/imunologia , Receptores Fc/metabolismo , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/metabolismo , Sequência de Bases , Primers do DNA/genética , Imunofluorescência , Humanos , Hibridomas/imunologia , Imunoglobulina M/metabolismo , Imunoprecipitação , Células Jurkat , Ligantes , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
7.
Curr Top Microbiol Immunol ; 382: 3-28, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25116093

RESUMO

IgM is the first Ig isotype to appear during phylogeny, ontogeny and the immune response. The importance of both pre-immune "natural" and antigen-induced "immune" IgM antibodies in immune responses to pathogens and self-antigens has been established by studies of mutant mice deficient in IgM secretion. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed, but fail to fully account for the IgM-mediated immune protection and regulation of immune responses. Particularly, the role of the Fc receptor for IgM (FcµR) in such effector functions has not been explored until recently. We have identified an authentic FcµR in humans using a functional cloning strategy and subsequently in mice by RT-PCR and describe here its salient features and the immunological consequences of FcµR deficiency in mice. Since the FcµR we cloned was identical to Toso or Fas inhibitory molecule 3 (FAIM3), there have been spirited debates regarding the real function of FcµR/Toso/FAIM3 and we will also comment on this topic.


Assuntos
Receptores Fc/fisiologia , Sequência de Aminoácidos , Animais , Éxons , Humanos , Imunoglobulina M/metabolismo , Camundongos , Dados de Sequência Molecular , Receptores Fc/análise , Receptores Fc/química , Receptores Fc/genética
8.
Int Immunol ; 26(12): 659-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24994818

RESUMO

The IgM-Fc receptor (FcµR) is involved in IgM homeostasis as evidenced by increased pre-immune serum IgM and natural auto-antibodies of both IgM and IgG isotypes in Fcmr-deficient C57BL/6 (B6) mice. To determine the impact of Fcmr-ablation on autoimmunity, we introduced the Fcmr null mutation onto the Fas-deficient autoimmune-prone B6.MRL Fas (lpr/lpr) mouse background (B6/lpr). Both IgM and IgG auto-antibodies against dsDNA or chromatin appeared earlier in FcµR(-) B6/lpr than FcµR(+) B6/lpr mice, but this difference became less pronounced with age. Splenic B2 cells, which were 2-fold elevated in FcµR(+) B6/lpr mice, were reduced to normal B6 levels in FcµR(-) B6/lpr mice, whereas splenic B1 cells were comparable in both groups of B6/lpr mice. By contrast, marginal zone (MZ) B cells were markedly reduced in FcµR(-) B6/lpr mice compared with either FcµR(+) B6/lpr or wild type (WT) B6 mice. This reduction appeared to result from rapid differentiation of MZ B cells into plasma cells in the absence of FcµR, as IgM antibody to a Smith (Sm) antigen, to which MZ B cells are known to preferentially respond, was greatly increased in both groups (B6/lpr and B6) of FcµR(-) mice compared with FcµR(+) B6/lpr or B6 mice. Mott cells, aberrant plasma cells with intra-cytoplasmic inclusions, were also increased in the absence of FcµR. Despite these abnormalities, the severity of renal pathology and function and survival were all indistinguishable between FcµR(-) and FcµR(+) B6/lpr mice. Collectively, these findings suggest that FcµR plays important roles in the regulation of auto-antibody production, Mott cell formation and the differentiation of MZ B cells into plasma cells in B6.MRL Fas (lpr/lpr) mice.


Assuntos
Formação de Anticorpos/imunologia , Autoanticorpos/imunologia , Autoimunidade/genética , Autoimunidade/imunologia , Plasmócitos/imunologia , Plasmócitos/metabolismo , Receptores Fc/deficiência , Animais , Autoanticorpos/sangue , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos MRL lpr , Camundongos Knockout , Nefrite/genética , Nefrite/imunologia , Nefrite/mortalidade , Nefrite/patologia , Plasmócitos/patologia , Receptores Fc/genética , Receptores Fc/metabolismo , Ribonucleoproteínas Nucleares Pequenas/imunologia
9.
J Clin Immunol ; 34 Suppl 1: S35-45, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24793544

RESUMO

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both pre-immune "natural" and antigen-induced "immune" IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed but fail to fully account for the IgM-mediated protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcµR). We have recently identified a bona fide FcµR in both humans and mice. In this article we briefly review what we have learned so far about FcµR.


Assuntos
Linfócitos B/imunologia , Imunoglobulina M/imunologia , Receptores Fc/imunologia , Animais , Autoantígenos/imunologia , Humanos , Imunomodulação , Camundongos , Receptores Fc/isolamento & purificação
11.
Proc Natl Acad Sci U S A ; 109(39): 15882-7, 2012 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-22984178

RESUMO

Cell surface Fc receptor for IgM antibody (FcµR) is the most recently identified member among FcRs. We determined the cellular distribution of mouse FcµR and the functional consequences of Fcmr disruption. Surface FcµR expression was restricted to B-lineage cells, from immature B to plasma cells, except for a transient down-modulation during germinal center reactions. Fcmr ablation had no significant effect on overall B- and T-cell development, but led to a reduction of marginal zone B cells and an increase in splenic B1 B cells. Preimmune serum IgM in mutant mice was significantly elevated as were natural autoantibodies. When immunized with live attenuated pneumococci, mutant mice mounted robust antibody responses against phosphorylcholine, but not protein, determinants compared with wild-type mice. By contrast, upon immunization with a hapten-carrier conjugate, nitrophenyl-coupled chicken γ-globulin (NP-CGG), the mutant mice had a diminished primary IgG1 response to both NP and CGG. These findings suggest that FcµR has an important role in IgM homeostasis and regulation of humoral immune responses.


Assuntos
Formação de Anticorpos/fisiologia , Diferenciação Celular/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Plasmócitos/imunologia , Receptores Fc/imunologia , Animais , Diferenciação Celular/genética , Homeostase/fisiologia , Imunoglobulina G/genética , Imunoglobulina M/genética , Camundongos , Camundongos Knockout , Plasmócitos/citologia , Receptores Fc/genética , Linfócitos T/citologia , Linfócitos T/imunologia
13.
J Immunol ; 179(4): 2105-14, 2007 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-17675469

RESUMO

CD4(+)CD25(+) regulatory T cells (Tregs) inhibit immune responses to a variety of Ags, but their specificity and mechanism of suppression are controversial. This controversy is largely because many studies focused on natural Tregs with undefined specificities and suppression has frequently been measured on polyclonal T cell responses. To address the issue of specificity further, we have bred K(d)-specific, CD4(+) TCR (TCR75) transgenic mice to Foxp3(gfp) knockin reporter mice to permit sorting of Tregs with a known specificity. Foxp3(gfp).TCR75 mice did not express significant numbers of natural FoxP3(+) Tregs expressing the TCR75 transgenes, but FoxP3 expression was induced by stimulating with K(d) plus TGF-beta. The resulting GFP(+) TCR75 cells were anergic, whereas the GFP(-) TCR75 cells proliferated upon restimulation with K(d) peptide. Yet both exhibited severely reduced expression of intracellular IFN-gamma and TNF-alpha upon restimulation. GFP(+), but not GFP(-), TCR75 T cells suppressed responses by naive TCR75 T cells and by nontransgenic spleen cells stimulated with anti-CD3. GFP(+) TCR75 cells also inhibited polyclonal C57BL/6 anti-K(d) CTL responses if the APC expressed K(d) and both MHC class I and class II, and responses by OT1 T cells to B6.K(d).OVA but not B6.K(d) plus OVA expressing APC, demonstrating linked-suppression of CD8 responses. Thus, Tregs exhibit a greater degree of specificity in vitro than previously appreciated. The observation that Tregs and responder T cells must recognize the same APC provides a mechanistic explanation for the observation that Tregs must be in direct contact with effector T cells to suppress their responses.


Assuntos
Antígenos/imunologia , Linfócitos T CD8-Positivos/imunologia , Fatores de Transcrição Forkhead/imunologia , Tolerância Imunológica/imunologia , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/imunologia , Regulação para Cima/imunologia , Animais , Anticorpos/imunologia , Anticorpos/farmacologia , Células Apresentadoras de Antígenos/imunologia , Antígenos/genética , Complexo CD3/imunologia , Proliferação de Células , Anergia Clonal/efeitos dos fármacos , Anergia Clonal/genética , Anergia Clonal/imunologia , Fatores de Transcrição Forkhead/genética , Genes Reporter/genética , Genes Reporter/imunologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/genética , Interferon gama/imunologia , Camundongos , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos T/genética , Fator de Necrose Tumoral alfa/imunologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
14.
Int Immunol ; 18(11): 1549-62, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16966495

RESUMO

Although CD4+CD25+FoxP3+ regulatory T cells play a role in allograft tolerance, the role of CD8+ cells with immunosuppressive function is less clear. To address this issue, spleen cells from Rag-1-deficient TCR transgenic (Tg) mice expressing a receptor for ovalbumin (OVA) in the context of MHC class I (OT1) were activated with OVA expressing antigen-presenting cell (APC) in the presence or absence of exogenous transforming growth factor beta (TGFbeta). TGFbeta inhibited the expression of IFN-gamma, granzyme B and the lytic activity of the OT1 T cells while inducing FoxP3 expression in 5-15% of the cells. By contrast, FoxP3 expression was not detected in naive OT-1 T cells or OT-1 T cells activated without exogenous TGFbeta. TGFbeta-activated OT1 cells inhibited the activation of Kd-specific CD8+ CTL responses by normal B6 T cells and the proliferation by Kd-specific CD4+ TCR Tg T cells, but only if the OVA epitope was co-expressed by Kd+ APC. This antigen-specific inhibitory activity, referred to as linked suppression, was neither mediated by residual lytic activity within the activated OT1 T cells nor did it depend upon IL-10 or TGFbeta. Suppression correlated with inhibition of CD86 expression on CD11c+ APC. TGFbeta-activated OT1 T cells also delayed the rejection of heterotopic, vascularized cardiac allografts mediated by anti-Kd-specific CD4+ TCR Tg T cells, but only if the cardiac allograft expressed both OVA and Kd as transgenes. Prolonged survival of allografts was associated with rapid migration of the FoxP3+ OT1 T cells into the donor heart raising the possibility that suppression may be mediated within the allograft. These data show that TGFbeta-activated CD8+ T cells mediate antigen-specific, APC-focused patterns of suppression in vitro and in vivo.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta/farmacologia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígeno B7-2/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição Forkhead/efeitos dos fármacos , Transplante de Coração/imunologia , Tolerância Imunológica/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos , Camundongos Transgênicos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
15.
Cell Immunol ; 230(1): 44-55, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15541718

RESUMO

T cells from TCR transgenic mice, expressing receptors specific for an allogeneic MHC class I peptide, were used to track T cell activation and migration in normal adoptive recipients that were subsequently transplanted with heterotopic hearts that were syngeneic except for a transgenic MHC class I antigen. T cells rapidly disappeared from the blood into the lymphoid tissues where they were activated within one day after transplantation. T cells initially formed discrete clusters in the spleen and lymph nodes. After proliferating for 2-4 days in lymphoid tissues, T cells reappeared in the blood and migrated to the heart and the intestines. The T cells underwent another round of proliferation in the heart, but not the intestines, and induced cardiac rejection uniformly on 6 day.


Assuntos
Movimento Celular , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Animais , Ciclo Celular , Proliferação de Células , Cinética , Linfonodos/citologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miocárdio/imunologia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Fase S , Baço/citologia , Baço/imunologia , Linfócitos T/metabolismo , Transplante Homólogo
16.
Am J Transplant ; 4(11): 1762-8, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15476474

RESUMO

Understanding the mechanisms of rejection of organs transplanted between unrelated individuals is confounded by the complexity of the alloantigens and the diversity of T cells responding to these alloantigens. To circumvent these problems, we developed a transgenic (Tg) C57BL/6 model system in which the T-cell receptor (TCR) expressed by CD4 T cells is specific for a defined allogeneic H-2Kd peptide and the cardiac donor expressed H-2Kd as a transgene on the C57BL/6 background (B6.Kd). These TCR Tg T cells were previously shown to mediate rapid rejection of a B10.D2 cardiac allograft when transferred to Rag1 recipients, demonstrating that the "indirect" pathway of allorecognition is sufficient for complete rejection in the absence of other T cells or antibody. Here, we report that B6.Kd hearts were rejected in an accelerated fashion by Rag1(-/-) TCR Tg T cells adoptively transferred to normal B6 recipients. Rejection in this model was associated with large myocardial infarcts and significant coronary artery inflammation. Moreover, transferred TCR Tg CD4+ cells mediated allograft injury without the requirement for cytotoxic function from recipient-derived CD8 T cells. A non-linear relationship was observed between the initial precursor frequency of the antigen-specific TCR Tg cells and the ultimate tempo of acute rejection, which is taken as evidence for cooperativity between components of the system.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Transplante Homólogo/imunologia , Transferência Adotiva , Animais , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Peptídeos/imunologia , Regiões Promotoras Genéticas , Baço/imunologia
17.
Transplantation ; 77(3): 452-5, 2004 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-14966425

RESUMO

The vast array of epitopes presented by allografts and the diversity of T cells responding to them complicates mechanistic studies of rejection. To minimize these problems, we developed a transgenic (Tg) model system limited to a single T-cell receptor (TCR)/peptide/major histocompatibility complex molecule. Two alloantigen-specific CD4 T-cell clones were used to isolate cDNA encoding the TCRalpha and TCRbeta chains that recognize the Kd54-68/I-Ab epitope. Two different TCR Tg lines were produced in C57BL/6 (B6) mice and crossed onto the B6.Rag1-/- background. B6.Rag1-/- recipients of T cells from TCR Tg Rag1-/-mice promptly rejected B10.D2, but not irrelevant B10.BR, cardiac grafts. Thus, a single allogeneic epitope presented by self-major histocompatibility complex class II is sufficient to activate TCR Tg T cells and serve as a target for rejection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Rejeição de Enxerto/imunologia , Transplante de Coração , Isoantígenos/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Animais , Circulação Coronária , Epitopos , Genes RAG-1 , Camundongos , Camundongos Endogâmicos C57BL/genética , Camundongos Knockout , Camundongos Transgênicos
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