Antigen Presentation by Dendritic Cells Focuses T Cell Responses Against Immunodominant Peptides: Studies in the Hen Egg-White Lysozyme (HEL) Model1

Gapin, Laurent; Alba, Yolanda Bravo de; Casrouge, Armanda; Cabaniols, Jean-Pierre; Kourilsky, Philippe; Kanellopoulos, Jean

doi:10.4049/jimmunol.160.4.1555

Cited by 58 publications

(1 citation statement)

References 79 publications

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“…( 34, 35 ) Kanellopoulos et al reported that DCs focused HEL-specific CD4 + T-cell responses against an I-E d -restricted peptide HEL103-117, while B cells presented an additional I-A d -restricted peptide HEL7-31. ( 36 ) Max Schnurr and colleagues had shown that CD1c + blood DCs and MoDCs were capable of presenting peptides of antigen NY-ESO-1 on both MHC I and MHC II, while pDCs were limited to MHC II presentation. ( 37 ) In this study, antigen UreB adjuvanted different adjuvants induced antigen-specific CD4 + T cell responses in vivo post-vaccination, whereas no peptides of UreB presented by A20 cells were detected in vitro using LC-MS/ MS. One reason may be differences in the cell types of APCs involved, with many APCs subtypes involved in vivo , especially DCs, but only the B cell line (A20) used in vitro .…”

Section: Discussionmentioning

confidence: 99%

PRR adjuvants restrain high stability peptides presentation on APCs

Li,

Zhang,

et al. 2024

Preprint

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Adjuvants can affect the function of APCs and boost the adaptive immune responses post vaccination. However, whether adjuvants modulate the specificity of immune responses, especially the specificity of immunodominant epitope responses, and the mechanisms of adjuvants regulating antigen processing and presentation remain poorly defined. Here, using overlapping synthetic peptides, we screened the dominant epitopes of Th1 responses in mice post vaccination with different adjuvants and found that adjuvants altered antigen-specific CD4+T cell immunodominant epitope hierarchy. MHC-II immunopeptidome demonstrates that peptide repertoires presented by APCs are altered by adjuvants significantly. Unexpectedly, no novel peptide presentation was detected post adjuvants treatment, on the contrary, peptides with high binding stability for MHC-II presented in the control group were missing post adjuvant stimulation, especially in the MPLA and CpG group. The low stability peptide presented in adjuvant groups elicited robust T cell responses effectively and formed immune memory. Taken together, our results suggest that adjuvants (MPLA and CpG) restrain high stability peptides presentation instead of revealing cryptic epitopes, which may alter the specificity of the CD4+T-cell dominant epitope responses. This capacity of adjuvants to modify pMHC stability and antigen-specific T cell immunodominant epitope responses has fundamental implications for the selection of suitable adjuvants in the vaccine design process and the development of epitope vaccines.

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Section: Discussionmentioning

confidence: 99%

PRR adjuvants restrain high stability peptides presentation on APCs

Li,

Zhang,

et al. 2024

Preprint

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T cell competition for the antigen-presenting cell as a model for immunodominance in the cytotoxic T lymphocyte response against minor histocompatibility antigens

et al. 1999

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We recently demonstrated that spleen cells primed against dominant BALB.B antigens can inhibit the cytotoxic T lymphocyte (CTL) response against subdominant antigens in vitro. In this study, we show that this interference is dependent on CD8+, but not CD4+, T cells directed against dominant antigens. Similar to immunodominance in vivo, T cell interference in vitro required presentation of dominant and sobdominant antigens by the same antigen‐presenting cell. In vivo priming with cells expressing dominant and subdominant antigens did not induce long‐lasting unresponsiveness against the latter. These results support a model in which immunodominance is mediated by T cell competition. In line with this, we found that the immunodominance effects in the CTL response against these minor histocompatibility antigens could be broken by immunization with live bone marrow‐derived dendritic cells.

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Enzyme‐Coated Mesoporous Silica Nanoparticles as Efficient Antibacterial Agents In Vivo

Wang

2013

Adv Healthcare Materials

128

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Despite the fact that pathogenic infections are widely treated by antibiotics in the clinic nowadays, the increasing risk of multidrug-resistance associated with abuse of antibiotics is becoming a major concern in global public health. The increased death toll caused by pathogenic bacterial infection calls for effective antibiotic alternatives. Lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) are reported as antibacterial agents that exhibit efficient antibacterial activity both in vitro and in vivo with low cytotoxicity and negligible hemolytic side effect. The Lys corona provides multivalent interaction between MSNs⊂Lys and bacterial walls and consequently raises the local concentration of Lys on the surface of cell walls, which promotes hydrolysis of peptidoglycans and increases membrane-perturbation abilities. The minimal inhibition concentration (MIC) of MSNs⊂Lys is fivefold lower than that of free Lys in vitro. The antibacterial efficacy of MSNs⊂Lys is evaluated in vivo by using an intestine-infected mouse model. Experimental results indicate that the number of bacteria surviving in the colon is three orders of magnitude lower than in the untreated group. These natural antibacterial enzyme-modified nanoparticles open up a new avenue for design and synthesis of next-generation antibacterial agents as alternatives to antibiotics.

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Antigen Presentation by Dendritic Cells Focuses T Cell Responses Against Immunodominant Peptides: Studies in the Hen Egg-White Lysozyme (HEL) Model1

Cited by 58 publications

References 79 publications

PRR adjuvants restrain high stability peptides presentation on APCs

PRR adjuvants restrain high stability peptides presentation on APCs

T cell competition for the antigen-presenting cell as a model for immunodominance in the cytotoxic T lymphocyte response against minor histocompatibility antigens

Enzyme‐Coated Mesoporous Silica Nanoparticles as Efficient Antibacterial Agents In Vivo

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