Selection of Similar Naive T Cell Repertoires but Induction of Distinct T Cell Responses by Native and Modified Antigen

Ria, Francesco; Gallard, Alexandra; Gabaglia, Claudia Raja; Guéry, Jean‐Charles; Sercarz, Eli E.; Adorini, Luciano

doi:10.4049/jimmunol.172.6.3447

Cited by 19 publications

(20 citation statements)

References 53 publications

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“…In general, destabilization of structure is associated with exposure of cryptic target sites and faster and more extensive digestion. Native and destabilized proteins vary with regard to their immunogenicity (55,62,69). Increases in structural flexibility and susceptibility to proteolysis are associated with a stronger and broader helper T-cell response (16,21,70), and change of a single cleavage site can dramatically influence the presentation of multiple T-cell epitopes (5).…”

Section: Discussionmentioning

confidence: 99%

Redirecting the Humoral Immune Response againstStreptococcus mutansAntigen P1 with Monoclonal Antibodies

et al. 2004

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The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.

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Section: Discussionmentioning

confidence: 99%

Redirecting the Humoral Immune Response againstStreptococcus mutansAntigen P1 with Monoclonal Antibodies

et al. 2004

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“…Repertoire analysis was performed using a modification of a described protocol (31). A total of 5 3 10 6 LNCs or 10 7 spleen-derived cells/well were cultured in the presence or absence of 10 mg/ml p139 for 3 d in RPMI 1640 medium (Sigma-Aldrich) supplemented with 2 mM L-glutamine, 50 mM 2-ME, 50 mg/ml gentamicin (Sigma-Aldrich), and 10% FCS (Life Technologies, Basel, Switzerland) (complete medium).…”

Section: Tcr Repertoire Analysismentioning

confidence: 99%

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

Nicolò¹,

Sali

Sante³

et al. 2009

The Journal of Immunology

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We infected SJL mice with a recombinant Mycobacterium smegmatis expressing a chimeric protein containing the self-epitope of proteolipid protein 139–151 (p139) fused to MPT64, a secreted protein of Mycobacterium tuberculosis (rMSp139). Infected mice developed a relapsing experimental autoimmune encephalomyelitis (EAE), showing a prevailing demyelination of the CNS, and disease severity was significantly lower in comparison with the one that follows immunization with p139. rMSp139 was not detected in lymph node or spleen in the course of clinical disease development or in the CNS during relapse. Infection with rMSp139 modified the p139-specific T cell repertoire, recruiting the spontaneous p139-specific repertoire and activating CD4+ T cells carrying the BV4 semiprivate rearrangement. T cells carrying the public BV10 rearrangement that are consistently found in the CNS during flares of disease were not activated by infection with rMSp139 because lymph node APCs infected with rMSp139 selectively fail to present the epitope for which BV10 cells are specific. Simultaneously, rMSp139 expanded p139-specific CD8+ cells more efficiently than immunization with peptide in adjuvant. SJL mice vaccinated against the CDR3 sequence of the BV10 public rearrangement reduced usage of the BV10 cells and displayed reduced symptoms during bouts of EAE. Thus, transient peripheral infection with a CNS-cross–reactive nonpathogenic Mycobacterium induces a relapsing EAE that continues long after clearance of the infectious agent. The composition of the self-reactive repertoire activated determines severity and histology of the resulting disease.

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“…Repertoire analysis was performed using a modification of a previously described protocol (26). Popliteal and inguinal LN cells were collected from mice and cultured for 3 days with or without mitomycin C (SigmaAldrich) treated 3T3-NKB cells (27) or 10 M peptides.…”

Section: Tcr Repertoire Analysismentioning

confidence: 99%

Distinct and Non-Overlapping T Cell Receptor Repertoires Expanded by DNA Vaccination in Wild-Type and HER-2 Transgenic BALB/c Mice

Rolla

Nicolò

Malinarich

et al. 2006

The Journal of Immunology

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Central tolerance to tumor-associated Ags is an immune-escape mechanism that significantly limits the TCR repertoires available for tumor eradication. The repertoires expanded in wild-type BALB/c and rat-HER-2/neu (rHER-2) transgenic BALB-neuT mice following DNA immunization against rHER-2 were compared by spectratyping the variable (V)β and the joining (J)β CDR 3. Following immunization, BALB/c mice raised a strong response. Every mouse used one or more CD8+ T cell rearrangements of the Vβ9-Jβ1.2 segments characterized by distinct length of the CDR3 and specific for 63-71 or 1206-1214 rHER-2 peptides. In addition, two CD4+ T cell rearrangements recurred in >50% of mice. Instead, BALB-neuT mice displayed a limited response to rHER-2. Their repertoire is smaller and uses different rearrangements confined to CD4+ T cells. Thus, central tolerance in BALB-neuT mice acts by silencing the BALB/c mice self-reactive repertoire and reducing the size of the CD8+ T cell component. CD8+ and CD4+ T cells from both wild-type and transgenic mice home to tumors. This definition of the T cell repertoires available is critical to the designing of immunological maneuvers able to elicit an effective immune reaction against HER-2-driven carcinogenesis.

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Selection of Similar Naive T Cell Repertoires but Induction of Distinct T Cell Responses by Native and Modified Antigen

Cited by 19 publications

References 53 publications

Redirecting the Humoral Immune Response againstStreptococcus mutansAntigen P1 with Monoclonal Antibodies

Redirecting the Humoral Immune Response againstStreptococcus mutansAntigen P1 with Monoclonal Antibodies

Mycobacterium smegmatisExpressing a Chimeric Protein MPT64-Proteolipid Protein (PLP) 139–151 Reorganizes the PLP-Specific T Cell Repertoire Favoring a CD8-Mediated Response and Induces a Relapsing Experimental Autoimmune Encephalomyelitis

Distinct and Non-Overlapping T Cell Receptor Repertoires Expanded by DNA Vaccination in Wild-Type and HER-2 Transgenic BALB/c Mice

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