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At least 631 records · Page 35Linked to original sources
PubMed1998

Development of a murine mutant Ras CD8+ CTL peptide epitope variant that possesses enhanced MHC class I binding and immunogenic properties.

We recently identified a murine mutant Ras p21 CD8+ CTL epitope reflecting residues 4 to 12, containing the mutation of Gly to Val at codon 12, that bound weakly to H-2Kd in vitro and generated a weak primary CTL response in immunized BALB/c mice. Here, we explored the hypothesis that specific modifications to the Ras4-12 peptide sequence can improve MHC binding, leading to enhanced immunogenicity without altering immune specificity. We synthesized Ras4-12 peptides in which Val at residue 12 was replaced with the more dominant H-2Kd C-terminus anchor residue Leu or Ile. In functional H-2Kd binding assays, Ras4-12(L12 or I12) peptide variants competed more effectively than the Ras4-12(V12) peptide. Ras4-12(L12 or I12) peptide variants enhanced both in vitro cytotoxicity and proliferation responses of anti-Ras4-12 CTL compared with the mutant Ras4-12(V12) peptide. Additionally, the Ras4-12(L12) peptide variant induced a quantitatively greater T cell response in vivo compared with that produced by Ras4-12(V12) as determined by IFN-gamma production. Mice immunized with Ras4-12(L12) peptide elicited CD8+ CTL activity specific for target cells presenting the Ras4-12(V12) epitope exogenously and endogenously. Moreover, both anti-Ras4-12(V12)-derived and anti-Ras4-12(L12)-derived CTL lines were similar insofar as their TCR usage and amino acid contact residues in the Ras4-12(V12) peptide. These experiments demonstrate that modifications can be introduced in tumor-specific peptide epitopes to enhance both in vitro and in vivo immunogenicity. The design of oncogene-specific peptide epitope variants as immunogens may accelerate the generation of anti-tumor T cell responses for cancer immunotherapy.

Amino Acid Substitution↗
PubMed1998

An alternative translational reading frame encodes an immunodominant retroviral CTL determinant expressed by an immunodeficiency-causing retrovirus.

Recognition of virus-infected or transformed cells by CD8+ CTL requires a trimolecular complex composed of MHC class I, beta2-microglobulin, and a specific foreign peptide composed of 8 to 10 linear amino acids. The generation of such CTL epitopes has traditionally been thought to be from the primary open reading frame encoding the viral or tumor-associated proteins. In this report it is demonstrated that a viral CTL epitope can also be generated from an alternative reading frame. Using a combination of synthetic peptides and Sindbis or vaccinia expression systems, MHC class I Kd-restricted BALB/cByJ CTL directed against defective gag gene constructs of the LP-BM5 virus complex that causes murine AIDS were shown to have specificity for the antigenic peptide SYNTGRFPPL. This epitope is generated in a novel fashion from the second open reading frame (ORF2) of both the defective and ecotropic helper virus components of LP-BM5. Importantly, lysis of target cells expressing BM5 ecotropic helper, and/or defective viral gag, demonstrated that the SYNTGRFPPL epitope is generated during the course of a normal retroviral infection. Furthermore, MAIDS-resistant BALB/cByJ mice also generated secondary restimulated CTL specific for SYNTGRFPPL following in vivo priming with the LP-BM5 retroviral complex. These data suggest that retroviruses, and potentially other viruses and foreign genes, are capable of expressing T cell epitopes from alternative open reading frames. If one considers the influence of self peptides on T cell development, these "alternative reading frame-derived" peptides could provide an important additional influence on the functional T cell repertoire.

Amino Acid Sequence↗
PubMed1998

Repeated intratracheal instillations of nonreplicating adenovirus 2 vector attenuate CTL responses and IFN-gamma production.

The proposed usage of replication-deficient adenovirus (Ad) vectors for corrective gene therapy or for mucosal immunization has been limited in part by the host reactivity to the Ad vector, thus limiting repeated Ad instillations. We have recently shown that the reactivity to the Ad vector is in large part due to increased CD4+ Th1 and Th2 responses as well as elevated IgG and mucosal IgA responses. It has been recently proposed that the diminution of transgene expression in respiratory epithelia was due to increased CTL reactivity to expressed Ad proteins. Herein, we report that repeated intratracheal delivery of a second generation Ad2 vector into mice results in no detectable CTL activity in freshly isolated lymphoid cells from lungs, lower respiratory lymph nodes, or spleens or after in vitro restimulation. In contrast, a single dose of Ad2 vector did elicit a robust CTL response. This attenuation of CTL activity was long lived and was not affected by macrophage depletion or due to a reduction in CD4+ or CD8+ T cells. Examination of cytokine production via MHC class I or class II restimulation by lymphoid cells from three intratracheally treated mice showed an attenuation in the production of IFN-gamma by as much as 110-fold. This reduction in IFN-gamma could not be attributed to increased IL-4 or IL-10 production. Thus, this study shows that the CTL response to Ad vectors is attenuated upon repeated administration.

Adenoviridae↗
PubMed1998

In vitro effects of IL-12 on HIV-1-specific CTL lines from HIV-1-infected children.

We studied the in vitro effects of IL-12 on HIV-1-specific CTL lines derived from PBMC of HIV-1-infected children. HIV-1-specific CTL lines were derived by limiting dilution following Ag-specific stimulation of PBMC from HIV-1-infected children and were maintained with repeated anti-CD3 stimulation. Following incubation with IL-12 for 5 to 7 days, HIV-1-specific cytotoxicity was augmented in a dose-dependent fashion (mean increase, 94 +/- 83 lytic units; p = 0.0006). Experiments performed with CD3-blocking Abs and MHC-mismatched targets demonstrated that the IL-12-enhanced activity was MHC restricted and dependent on cells bearing CD3. The effect of IL-12 on proliferation of the CTL lines as tested by [3H]TdR uptake was minimal, with stimulation indexes ranging from 1.25 to 4.9. The effects of IL-12 on cytotoxicity were not significantly altered by addition of Ab to the IL-2R (anti-Tac) in quantities sufficient to block exogenous IL-2 (p = 0.15), demonstrating that endogenous IL-2 activity is not required for IL-12-enhanced cytolytic activity. Likewise, addition of neutralizing Ab specific for IFN-gamma did not change IL-12-enhanced cytotoxicity (p = 0.61). The in vivo role of IL-12 in the generation and the stimulation of CTL remains to be determined; however, its ability to augment HIV-1-specific CTL in vitro adds additional support for IL-12 as a candidate for immune-based therapy of HIV-1.

Adolescent↗
PubMed1998

Th2-type CD4+ cells neither enhance nor suppress antitumor CTL activity in a mouse tumor model.

Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.

Adjuvants, Immunologic↗
PubMed1998

The regulation of CD95 ligand expression and function in CTL.

Previous studies with CTL lines and CTL hybridomas have suggested that functional CD95 (APO-1/Fas)-ligand (CD95L) expression on effector CTLs is a consequence of specific CTL-target recognition and TCR triggering of newly transcribed CD95L. Such a control on the expression of CD95L could provide a double safeguard for killing only cognate target cells. Here the regulation of CD95L expression and function was tested in in vivo primed, alloreactive peritoneal exudate CTL (PEL) from perforin-deficient (P0) mice. CD95L-based, PEL-mediated cytotoxicity was blocked by brefeldin A, an inhibitor of intracellular protein transport, but not by the protein synthesis inhibitor emetine, the immunosuppressive drug cyclosporin A, or the DNA transcription inhibitor actinomycin D. CD95L mRNA transcripts in freshly isolated PEL were shown by RT-PCR; CD95L surface expression was evident by staining with Fas-Fc as well as CD95L Abs. Undiminished CD95L expression and cytocidal activity were found in PEL incubated for 48 h in culture, without adding Ag, mitogen, or cytokines. PEL expressed functional CD95L, yet exhibited target cell-specific killing, except when encountering high CD95-expressing cells. The results indicate that PEL use CD95L probably expressed in the Golgi and/or on the cell surface and do not require newly transcribed CD95L upon target cell conjugation. Hence the TCR-triggered recruitment of preformed CD95L, rather than its biosynthesis, controls CD95L-based specific lysis induced by CTL.

Animals↗
PubMed1998

Human class I supertypes and CTL repertoires extend to chimpanzees.

Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses to several HBV-encoded epitopes that are known to be recognized by class I-restricted CTL in acutely infected humans. One animal responded to three HBV peptides that, in humans, are restricted by HLA-A2; the other animal responded to three peptides that are restricted by HLA-B35 and HLA-B51, members of the HLA-B7 supertype in man. The peptides recognized by each chimp corresponded with the ability of its class I molecules to bind peptides containing the HLA-A2 and HLA-B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of these peptides were also detected in occasional HBV-uninfected chimps. These results demonstrate that the CTL repertoire overlaps in humans and chimps and that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these results, the immunogenicity and efficacy of vaccines designed to induce CTL responses to human HLA-restricted viral epitopes may be testable in chimpanzees.

Amino Acid Sequence↗
PubMed1999

Cutting edge: induction of enhanced CTL-dependent protective immunity in vivo by N-end rule targeting of a model tumor antigen.

There is much interest in vaccines that will enhance the induction of CTL. One mechanism to enhance Ag-specific CTL responses involves targeting Ag to undergo rapid cytoplasmic degradation by the N-end rule pathway. We have analyzed the ability of N-end rule targeting to confer protection in an immunization-challenge setting. Using the HIV-1 nef protein as a model tumor Ag, we found that in mice immunized with a vaccinia vector expressing a form of nef that is targeted for rapid cytoplasmic degradation, there was enhanced induction of nef-specific CTL and protection from a lethal challenge with the syngeneic CT26 tumor cells that had been transfected with nef. Protection from tumor challenge correlated with the magnitude of the CTL response. Thus, the targeting of tumor or viral Ags for rapid cytoplasmic degradation by the N-end rule pathway may represent a strategy for the induction of protective Ag-specific CTL responses in vivo.

Adenocarcinoma↗
PubMed1999

Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees.

Certain HIV-1 infected humans that do not progress to AIDS have been documented to share particular MHC class I alleles that appear to correlate with long-term survival. HIV-1-infected chimpanzees are relatively resistant to progression to AIDS. Out of a group of 10 chimpanzees with CTL activity and nonprogressive HIV-1 infection, 2 animals with prominent cytolytic CD3+CD8+ T cell responses to HIV-1 Ags were studied in detail. Characterization of these CTL revealed that they contained the granzymes A and B, T cell intracellular Ag-1, and perforin and induced calcium-dependent cytolysis that correlated with the presence of apoptotic nuclei in target cells. These CTL responses were directed against two gagpeptides, which were found to be identical to previously described epitopes recognized in the context of HLA-B27 and HLA-B57 molecules. The latter two restriction elements occur with increased frequency in human long-term survivor cohorts. Phylogenetic comparisons revealed that the chimpanzee restriction elements, Patr-B*02and -B*03, described here do not show any obvious similarity with the HLA-B*27 and -B*57 alleles, suggesting that CTL responses to HIV-1 in distinct primate species may be controlled by different types of HLA-B-like molecules. The CTL responses in these two chimpanzees are directed, however, against highly conserved epitopes mapping across the majority of HIV-1 clades.

Acquired Immunodeficiency Syndrome↗
PubMed1999

MHC class I-restricted epitope spreading in the context of tumor rejection following vaccination with a single immunodominant CTL epitope.

Epitope spreading is a process whereby epitopes distinct from and non-cross-reactive with an inducing epitope become targets of an evolving immune response. This phenomenon has been associated most notably with the progression of naturally occurring or experimentally induced chronic autoimmune diseases. We have investigated the potential occurrence of epitope spreading in the context of antitumor cytotoxic T cell (CTL) responses using chicken ovalbumin (OVA) as a model antigen. Our results indicate that following rejection of OVA-expressing EG.7 tumor cells effectuated by a CTL response which is induced against the MHC class I-restricted immunodominant epitope OVA257-264, there occurs intramolecular diversification of the CTL response to two additional OVA-derived epitopes, OVA176-183 and OVA55-62, as well as intermolecular spreading to other endogenous tumor-derived determinants. It seems that CTL-mediated tumor cell destruction in vivo favors cross-presentation of additional epitopes with the consequent activation of additional tumor-reactive lymphocytes. The process of epitope spreading in that context has obvious important implications for the design of antigen-specific antitumor immunotherapies.

Animals↗
PubMed2000

A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules.

Although it is known that a single peptide can be recognized by CTL restricted to two MHC class I alleles, there is no direct evidence for presentation of a single peptide by two MHC class I molecules. Furthermore, it is unclear whether such peptides are presented to the same T cell or to different T cells. Our previous study suggested that CTL recognition of the human immunodeficiency virus-1 (HIV-1) Pol HIV-B35-SF2-24 epitope (IPLTEEAEL) occurs via both HLA-B35 and HLA-B51 restriction. Here we provide the first direct evidence that a single CTL clone can recognize this peptide presented by both HLA-B35 and HLA-B51. Furthermore, we directly purified this peptide eluted from both HLA-B*3501 and HLA-B*5101 molecules isolated from target cells infected with HIV-1 recombinant vaccinia virus. These results demonstrate that HIV-B35-SF2-24 is a naturally processed peptide which is presented by both HLA-B*3501 and HLA-B*5101. TCR analysis of one CTL clone suggested that it is a single clone. B*3501-SF2-24-tetrameric complexes inhibited both HLA-B*3501- and HLA-B*5101-restricted recognition of this clone, suggesting that the TCR of this clone cross-recognize the structure of both HLA class I-peptide complexes.

Amino Acid Sequence↗
PubMed2001

CTL activation is induced by cross-linking of TCR/MHC-peptide-CD8/p56lck adducts in rafts.

To investigate the role of the coreceptor CD8 and lipid rafts in cytotoxic T lymphocyte (CTL) activation, we used soluble mono-and multimeric H-2Kd-peptide complexes and cloned S14 CTL specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite (PbCS) peptide 252-260 [PbCS(ABA)]. We report that activation of CTL in suspension requires multimeric Kd-PbCS(ABA) complexes co-engaging TCR and CD8. Using TCR ligand photo-cross-linking, we find that monomeric Kd-PbCS(ABA) complexes promote association of TCR/CD3 with CD8/p56lck. Dimerization of these adducts results in activation of p56lck in lipid rafts, where phosphatases are excluded. Additional cross-linking further increases p56lck kinase activity, induces translocation of TCR/CD3 and other signaling molecules to lipid rafts and intracellular calcium mobilization. These events are prevented by blocking Src kinases or CD8 binding to TCR-associated Kd molecules, indicating that CTL activation is initiated by cross-linking of CD8-associated p56lck. They are also inhibited by methyl-beta-cyclodextrin, which disrupts rafts and by dipalmitoyl phosphatidylethanolamine, which interferes with TCR signaling. Because efficient association of CD8 and p56lck takes place in rafts, both reagents, though in different ways, impair coupling of p56lck to TCR, thereby inhibiting the initial and essential activation of p56lck induced by cross-linking of engaged TCR.

Animals↗
PubMed2003

Identification of a CTL-directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region: a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients.

Although cytotoxic T lymphocyte (CTL)-directed epitopes binding to human histocompatibility leukocyte antigen (HLA)-A molecules have been well characterized, those binding to HLA-B molecules have not, largely due to their large diversity. In this study we report a unique cancer antigen gene, tentatively named Testin-related gene (TRG), which encodes CTL-directed epitopes on the HLA-B52 molecules most frequently expressed in Asians. TRG is located in an intron of the putative tumor suppressor gene Testin in the common fragile site 7G region at 7q31.2. TRG mRNA was expressed in the majority of cancer cells and cancer tissue tested, whereas it was scarcely expressed in the majority of normal tissues, and only low-level expression of TRG was detected in the heart, liver, and pancreas. One TRG peptide had the ability to induce HLA-B52-restricted CTL cytotoxic to TRG+ tumor cells in peripheral blood mononuclear cells (PBMC) of epithelial cancer patients. This peptide also induced HLA-B62-restricted and tumor-reactive CTL in PBMC of cancer patients. Therefore, this TRG-derived peptide might be appropriate for use in peptide-based immunotherapy for relatively large numbers of cancer patients throughout the world, given that 34% of Japanese, 27% of Chinese, and 13% of Caucasians express either HLA-B52 or HLA-B62 molecules

Cancer Vaccines↗
PubMed2003

Comparative analysis of NK- or NK-CTL-mediated lysis of immature or mature autologous dendritic cells.

Natural killer (NK) cells have been shown to kill efficiently autologous immature dendritic cells (iDC), while sparing those undergone maturation. In this study we investigated the effect of the interaction between autologous DC and NK-cytolytic T lymphocytes (NK-CTL), a subset of HLA-E-restricted CD8(+) T cells that express HLA class I-specific inhibitory NK receptors. Although these cells share with NK cells various phenotypic and functional features (such as the capacity to lyse most allogeneic, NK-susceptible tumor cell lines), different from NK cells, NK-CTL failed to lyse autologous DC. However, after pulsing DC with a cytomegalovirus-derived, HLA-E-binding peptide recognized by NK-CTL, both iDC and mature DC became highly susceptible to lysis. On the other hand,the addition of the peptide resulted in the down-regulation of the NK-mediated lysis of the same autologous iDC. The capability of killing autologous DC, presenting a non-self, HLA-E-binding peptide, may represent a feedback mechanism by which NK-CTL down-regulate HLA-E-restricted responses to certain pathogens.

Cells, Cultured↗
PubMed2005

Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy.

Animals↗
PubMed1993

T-cell-receptor engagement and tumor ICAM-1 up-regulation are required to by-pass low susceptibility of melanoma cells to autologous CTL-mediated lysis.

Tumor-specific and non-specific CD3+, TcR alpha beta+, CD8+ cytotoxic T-cell (CTL) clones, isolated from tumor-infiltrating lymphocytes (TIL) or peripheral blood lymphocytes (PBL) of a melanoma patient and allogeneic LAK cells, were used to investigate the requirements for bypassing the low lysability of some melanoma clones derived from an s.c. metastasis from which highly lysable clones were also obtained. Cytofluorimetric analysis showed that all melanoma clones expressed ICAM-1, although to different extents, reaching a 10-fold difference in fluorescence units, while HLA class-I antigens were similarly expressed. The differences in expression of ICAM-1 among tumor clones correlated with differences in lysability, by both specific and non-specific CTL, but were not large enough to affect lymphocyte-tumor conjugate formation. Cytokine- or gene-transfer-mediated up-regulation of ICAM-1 did not induce de novo lysis of ICAM-1low tumor cells; however, it markedly enhanced a low level of killing of the same cells by tumor-specific, TcR-dependent and HLA-restricted CTL clones but not by non-specific, TcR-independent effectors. In addition, lysis of melanoma clones by any effector was similarly inhibited by anti-ICAM-1 and anti-LFA-1 antibodies. This indicates that by-pass of low lysability of ICAM-1low melanoma clones by CTL clones, after ICAM-1 up-regulation, is possible only if simultaneous LFA-1 and TcR engagement takes place. In addition, these results suggest that the constitutive high level of expression of ICAM-1 on the subset of ICAM-1high melanoma cells must be only one of the factors contributing to the high lysability of these cells by any effector.

Cell Adhesion Molecules↗
PubMedDate not supplied

Use of a lentiviral flap vector for induction of CTL immunity against melanoma. Perspectives for immunotherapy.

BACKGROUND: A central triple-stranded DNA structure created during HIV-1 reverse transcription, the central flap, acts as a cis-active nuclear import determinant of the HIV-1 DNA genome. Insertion of the sequences responsible for formation of the central DNA flap into an HIV-1-derived vector strongly enhances its transduction efficiency. METHODS: HIV-1 vectors with or without inclusion of the DNA flap and encoding the same melanoma polyepitope were constructed to transduce dendritic cells (DCs) and to evaluate their capacity for induction of melanoma-specific cytotoxic T-lymphocyte (CTL) responses ex vivo and in vivo. RESULTS: HIV-1 vectors including the DNA flap transduced up to 100% of immature mouse and human DCs. Inoculation of HLA-A2.1 transgenic mice with this flap vector elicited vigorous and multi-specific long-term anti-melanoma CTL responses, whereas the parental vector lacking the flap sequence was less efficient. Furthermore, human DCs transduced ex vivo with the recombinant DNA flap vector displayed efficient multi-specific primary human CTL responses against melanoma. CONCLUSION: Lentiviral vectors including the DNA flap should be powerful tools both for active immunization and for the ex vivo priming of CTL for tumor immunotherapy.

Animals↗
PubMed1999

Immunization with dendritic cells breaks immunodominance in CTL responses against minor histocompatibility and synthetic peptide antigens.

We have examined the mechanisms involved in immunodominance in two different experimental models: the cytotoxic T lymphocyte (CTL) response in B6 mice against minor histocompatibility antigens of BALB.B mice, and the response of B6 mice against a mixture of five synthetic peptides corresponding to well-defined immunogenic epitopes. The CTL responses in these models focus on a few dominant epitopes, whereas no or only weak responses can be detected against other subdominant epitopes. Neither of these immunodominance phenomena can be explained by insufficient presentation of subdominant epitopes in the presence of the dominant ones. Immunodominance could also be demonstrated in an in vitro system, in which B6 splenocytes primed with BALB.B could interfere with the CTL response against subdominant antigens. This interference was dependent on CD8+ T cells and on the simultaneous presentation of dominant and subdominant antigens on the same antigen-presenting cell, suggesting T cell competition around the antigen-presenting cell as a potential explanation. The immunodominance in both systems could be broken by immunization with dendritic cells (from BALB.B or from B6 loaded with peptides). This procedure allowed detection of CTL responses against both dominant and previously subdominant antigens.

Animals↗