Co-Receptors and Recognition of Self at the Immunological Synapse

Gascoigne, Nicholas R. J.; Żal, Tomasz; Yachi, Pia P.; Hoerter, John A. H.

doi:10.1007/978-3-642-03858-7_9

Cited by 18 publications

(23 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under these conditions, requisite cell surface molecules on APC that are required for continued expansion of CD4 T cells specific for subdominant peptides may become limiting. This idea is supported by published data that suggest that non-cognate and endogenous pMHC molecules accumulate within the immunological synapse (39). To evaluate trogocytosis, the level of several cell surface molecules on peptide-loaded DC was quantified over time within dLNs over the course of the immune response.…”

Section: Resultssupporting

confidence: 59%

Orchestration of CD4 T Cell Epitope Preferences after Multipeptide Immunization

Tung

Sant

2013

The Journal of Immunology

View full text Add to dashboard Cite

A detailed understanding of the molecular and cellular mechanisms that underlie epitope preferences in T cell priming is important for vaccines designed to elicit a broad T cell response. Protein vaccinations generally elicit CD4 T cell responses that are skewed toward a small fraction of epitopes, a phenomenon known as immunodominance. This characteristic of T cell responses, that limits the diversity of CD4 T cell recognition, is generally attributed to intracellular antigen processing. However, we recently discovered that immunodominance hierarchies persist even after vaccination with synthetic peptides. In this study, we probed the regulatory mechanisms that cause diminished CD4 T cell responses to subdominant peptides after such multi-peptide immunization in mice. We have found that the delivery of subdominant and dominant epitopes on separate dendritic cells rescues expansion of less favored CD4 T cells. Furthermore, through the use of genetic models and inhibitors, we have found that selective losses in CD4 T cell responses are mediated by an IFN-γ-induced pathway, involving indoleamine 2,3-dioxygenase (IDO), and that regulatory T cell (Treg) activities may also regulate preferences in CD4 T cell specificity. We propose that after multi-peptide immunization, the expansion and differentiation of dominant T cells initiate complex regulatory events that determine the final peptide specificity of the elicited CD4 T cell response.

show abstract

Section: Resultssupporting

confidence: 59%

Orchestration of CD4 T Cell Epitope Preferences after Multipeptide Immunization

Tung

Sant

2013

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…There are two aspects of this that have been explored –the contribution of self-pMHC recognition during foreign antigen encounter itself, and the effects of self-pMHC on intrinsic properties of naïve T cells prior to encounter with foreign antigen. Davis and colleagues first introduced the concept that non-stimulatory self-pMHC complexes may serve as “co-agonists” to assist the T cell response to foreign pMHC ligands 82, 83 . However, it remains unclear whether co-agonists contribute to all T cell responses, and even in situations where a co-agonist role could be observed there was considerable controversy over whether co-agonist encounters were peptide specific or not, with divergent conclusions being drawn for CD4 and CD8 T cells 82, 83 .…”

Section: Self-sensitivity Regulates Foreign Antigen Reactivitymentioning

confidence: 99%

“…Davis and colleagues first introduced the concept that non-stimulatory self-pMHC complexes may serve as “co-agonists” to assist the T cell response to foreign pMHC ligands 82, 83 . However, it remains unclear whether co-agonists contribute to all T cell responses, and even in situations where a co-agonist role could be observed there was considerable controversy over whether co-agonist encounters were peptide specific or not, with divergent conclusions being drawn for CD4 and CD8 T cells 82, 83 . A recent report from Gascoigne’s group nicely resolves this discrepancy by showing that there are two modes of co-agonist contribution, in which the significance of the TCR affinity for the co-agonist pMHC depends critically on the strength of co-receptor binding to the foreign pMHC target 84 – since the CD8 co-receptor is thought to have a higher affinity for Class I MHC molecules (albeit not all alleles) compared to the CD4-Class II MHC interaction, TCR specificity for co-agonist ligands may be a much more stringent limitation for CD4 compared to CD8 T cells 84 .…”

Section: Self-sensitivity Regulates Foreign Antigen Reactivitymentioning

confidence: 99%

The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function

2014

View full text Add to dashboard Cite

Self-reactivity was once seen as a potential characteristic of T cells that was eliminated by clonal selection to protect the host from autoimmune pathology. We now appreciate that the T cell repertoire is in fact, broadly self-reactive, one could even say self-centered. The strength with which a T cell reacts to self ligands, and the environmental context that this reaction occurs in, influences almost every aspect of T cell biology: from development to differentiation to effector function. In this review we highlight recent advances and discoveries that relate to T cell self-reactivity, with a particular emphasis on TCR signaling thresholds.

show abstract

“…4). This was not unexpected, since dispase-mediated cleavage of key surface molecules including the two co-receptors CD4 and CD8 on T cells may directly hamper optimal formation of the immunological synapse, thereby interfering with T cell receptormediated recognition of MHC/peptide complexes on the surface of antigen presenting cells [20]. In addition, molecules such as CD27 and the high-affinity IL-2 receptor CD25 (and possibly other important receptors not included in this survey) were found to be extremely sensitive to dispase treatment, which may have direct effects on the expansion and survival of activated T cells [21,22].…”

Section: High Dose Dispase Treatment Impairs Antigen Specific Cd4+ Anmentioning

confidence: 99%

Impact of enzymatic tissue disintegration on the level of surface molecule expression and immune cell function

Autengruber¹,

Gereke²,

Hansen³

et al. 2012

European Journal of Microbiology and Immunology

143

109

View full text Add to dashboard Cite

Immunological characterization of immune cells that reside in specific anatomic compartments often requires their isolation from the respective tissue on the basis of enzymatic tissue disintegration. Applying enzymatic digestion of primary splenocytes, we evaluated the impact of collagenase and dispase, two enzymes that are commonly used for the liberation of immune cells from tissues, on the detectability of 48 immunologically relevant surface molecules that are frequently used for flow cytometric identification, isolation, and characterization of immune cell subsets. Whereas collagenase treatment had only minor effects on surface expression of most molecules tested, dispase treatment considerably affected antibody-mediated detectability of the majority of surface markers in subsequent FACS analyses. This effect was long lasting and, in case of high-dose dispase treatment, evident for the majority of surface molecules even after 24 h of in vitro culture. Of note, high-dose dispase treatment not only affected surface expression of certain molecules but also impaired antigen-specific proliferation of CD4 + and CD8 + T cells. Together, our data indicate that enzymatic tissue disintegration can have profound effects on the expression of a variety of cell-surface molecules with direct consequences for phenotypic analysis, FACS-and MACS-based target cell isolation, and immune cell function in cell culture experiments.

show abstract

Co-Receptors and Recognition of Self at the Immunological Synapse

Cited by 18 publications

References 73 publications

Orchestration of CD4 T Cell Epitope Preferences after Multipeptide Immunization

Orchestration of CD4 T Cell Epitope Preferences after Multipeptide Immunization

The self-obsession of T cells: how TCR signaling thresholds affect fate 'decisions' and effector function

Impact of enzymatic tissue disintegration on the level of surface molecule expression and immune cell function

Contact Info

Product

Resources

About