Serial triggering of many T-cell receptors by a few peptide–MHC complexes

Valitutti, Salvatore; Müller, Sabina; Cella, Marina; Padovan, Elisabetta; Lanzavecchia, Antonio

doi:10.1038/375148a0

Cited by 1,050 publications

(946 citation statements)

References 25 publications

Supporting

Mentioning

879

Contrasting

Unclassified

Order By: Relevance

“…This could result in the engagement of a higher number of TCR and other molecules on the surface of the T cell that are engaged in generating the activation signal cascade [36]. T cells have been found to "count" the number of TCR that are involved in the interaction with the APC, and a T cell becomes activated once a critical threshold number is reached [37,38]. In the case of such enhanced membrane interactions, DC should be able to more rapidly engage the critical number of TCR compared to B cells.…”

Section: Discussionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

View full text Add to dashboard Cite

It is unknown to what extent the heterogeneity of antigen presenting cells (APC) influences the IFN-γ response of CD4 memory cells. We restimulated DO11.10 T cell receptor (TCR)-transgenic cells and wild-type CD4 memory cells with OVA-peptide 323 -339 presented on purified dendritic cells (DC), macrophages, and B cells. Using IFN-γ ELISPOT assays we measured the number of cytokine producing T cells and the amount of cytokine produced by individual T cells at different time points after antigen encounter. The data showed that, when CD4 cells recognized antigen on DC, the induction of cytokine production was accelerated compared to macrophages and B cells. In contrast, the per-cell cytokine productivity was independent of the type of APC by which the T cells were restimulated. Moreover, the peptide concentration required for CD4 cell activation was comparable for the different APC. The data suggest that DC induce cytokine production in memory cells with accelerated activation kinetics, whereas 24 h of antigen stimulation on DC, macrophages, and B cells results in comparable levels of T cell activation. These data have implications for the understanding of T cell memory responses when T cells re-encounter antigen on different APC as well as for the monitoring of memory T cell responses ex vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…peptides bound to MHC molecules expressed on APC [27,28]. The extent of TCR downregulation is dependent on the concentration and quality of the agonist displayed on the APC surface, but is not influenced by costimulatory molecules [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…Second, we evaluated the response to the melanoma target in terms of TCR down-regulation. For this experiment, we chose the only melanoma patient whose PHA line exhibited some degree of TCR downregulation versus the natural Melan-A [26][27][28][29][30][31][32][33][34][35] peptide, a prerequisite for melanoma cell recognition, and we selected the vitiligo patient exhibiting the most similar behavior. The results indicated that only vitiligo CTL were capable of TCR down-regulation in response to this stimulus (Fig.…”

Section: Tumor Reactivity Of Whole Melan-a-specific Cytotoxic T Lymphmentioning

confidence: 99%

Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo

et al. 2005

View full text Add to dashboard Cite

Vitiligo is a skin disorder characterized by depigmented macules secondary to melanocyte loss. An unusual facet is its relation to melanoma: Cytotoxic T lymphocytes directed to melanocyte antigens are found in both conditions and imply a breakdown of tolerance, yet the resulting immune reaction is the opposite. The mechanisms at the basis of these opposite effects are not known. Here, we performed a direct comparison of whole melanocyte-specific T cell populations in the two diseases. We demonstrate that neither precursor frequencies of Melan-A/MART-1-specific T lymphocytes nor their status of activation differ significantly. However, by using a tetramer-based T cell receptor down-regulation assay, we documented a higher affinity of vitiligo T cells. We calculated that the peptide concentration required for 50% of maximal receptor downregulation differed by 6.5-fold between the two diseases. Moreover, only vitiligo T cells were capable of efficient receptor down-regulation and IFN-c production in response to HLA-matched melanoma cells, suggesting that this difference in receptor affinity is physiologically relevant. The differences in receptor affinity and tumor reactivity were confirmed by analyzing Melan-A/MART-1-specific clones established from the two diseases. Our results suggest that the quality, and not the quantity, of the melanocytespecific cytotoxic responses differs between the two pathologies.

show abstract

“…In contrast, fibroblasts, muscle cells, and liver hepatocytes carry much lower quantities, sometimes 100 or fewer per cell. It was estimated that APC pulsed with high concentration (20 μM) of peptide displays ~7500 pMHC-I complex, and with low concentration (50 nM) display only ~100 pMHC-I complex (45). Normally, each nucleated cell expresses 4~6 different kinds of MHC-I.…”

Section: Molecular Basis Of Mhc-i/tcr Interactionmentioning

confidence: 99%