Immunodomination results from functional differences between competing CTL

Roy-Proulx, Guillaume; Meunier, Marie-Christine; Lanteigne, Anne-Marie; Brochu, Sylvie; Perreault, Claude

doi:10.1002/1521-4141(200108)31:8<2284::aid-immu2284>3.0.co;2-e

Cited by 30 publications

(17 citation statements)

References 47 publications

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“…In contrast, HY MiHA elicits CD8 T cell responses only when presented alone. H7 a totally abrogates responses to HY when both Ags are presented on the same APC (16,19). We found that the differentiation programs of anti-H7 a and anti-HY T cells were similar, but did not progress simultaneously.…”

mentioning

confidence: 63%

“…Thus, with this immunization scheme, each population of APC triggered CD8 T cells specific for a single MHC class I-associated epitope. Recognition of B10.H7 b male splenocytes led to expansion of CD8 T cells specific for the H2D b -restricted HY Ag, whereas B10 male APC entailed selective expansion of CD8 T cells specific for the H2D b -restricted H7 a Ag (16,19,22,26,27). Of note, both populations of Ag-specific CD8 T cells received CD4 help solely from CD4 T cells specific for the MHC class II-restricted HY Ag (31).…”

Section: Immunization and Design Of Microarray Experimentsmentioning

confidence: 99%

“…Several nonmutually exclusive explanations have been proposed for this. Dominating T cells may kill or exhaust APCs, monopolize APC resources, or directly send inhibitory signals to nondominant T cells (7,15,19,22,23). Two studies reported that injection of very large numbers of memory CD8 T cells specific for immunodominated Ag did not enable these T cells to compete more successfully against T cells that recognized dominant epitopes (14,24).…”

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confidence: 99%

“…Thus, except perhaps in some extreme situations, dominating T cells do not win the competition at the T cell/APC interface because they are more abundant than other T cell clonotypes in preimmune animals (23). Dominating T cells win the competition because they possess some elusive functional advantage over other T cells (14,19,23).…”

mentioning

confidence: 99%

“…We rationalized that selecting these Ags would maximize the sensitivity of our studies because H7 a and HY lie at opposite ends of the immunodomination scale (that is, in their ability to exert and resist immunodomination). Thus, while cell surface expression of H7 a prevents priming against many MiHAs present on C57BL/6 cells, H7 a -specific CD8 T cells consistently resist immunodomination by T cells specific for a myriad of other MiHAs (16,19,22). In contrast, HY MiHA elicits CD8 T cell responses only when presented alone.…”

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confidence: 99%

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Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens

Baron

Meunier

Caron

et al. 2006

The Journal of Immunology

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Restriction of T cell responses to a few epitopes (immunodominance) is a central feature of immune responses. We analyzed the entire transcriptome of effector CD8 T cells specific for a dominant (H7a) and a cryptic (HY) mouse Ag and performed a longitudinal analysis of selected T cell differentiation markers. We found that Ag specificity had a relatively modest influence on the repertoire of genes that are transcriptionally modulated by the CD8 T cell differentiation program. Although the differentiation programs of anti-H7a and anti-HY T cells were similar, they did not progress simultaneously. The expansion peak of anti-H7a T cells was reached on day 10 while that of anti-HY T cells was attained on days 15–20. Between days 10 and 20, anti-H7a T cells were in the contraction phase and anti-HY T cells in the expansion phase. Furthermore, expansion and development of effector function were well-synchronized in anti-H7a T cells but were disconnected in anti-HY T cells. We propose that, by leading to selective expansion of the fittest CD8 T cells, immunodominance may be beneficial to the host. Inhibition of the T cell response to cryptic Ag would ensure that host resources (APC, cytokines) for which T cells compete are devoted to T cells with the best effector potential. One implication is that favoring expansion of the fittest effector T cells in general may be more important than increasing the diversity of the T cell repertoire.

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confidence: 63%

Section: Immunization and Design Of Microarray Experimentsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Asynchronous Differentiation of CD8 T Cells That Recognize Dominant and Cryptic Antigens

Baron

Meunier

Caron

et al. 2006

The Journal of Immunology

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CD8⁺ T‐cell cross‐competition is governed by peptide–MHC class I stability

et al. 2011

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A major contributing factor to the final magnitude and breadth of CD8+ T-cell responses to complex antigens is immunodomination, where CD8+ T cells recognizing their cognate ligand inhibit the proliferation of other CD8+ T cells engaged with the same APC. In this study, we examined how the half-life of cell surface peptide–MHC class I complexes influences this phenomenon. We found that primary CD8+ T-cell responses to DNA vaccines in mice are shaped by competition among responding CD8+ T cells for nonspecific stimuli early after activation and prior to cell division. The susceptibility of CD8+ T cells to ‘domination’ was a direct correlate of higher kinetic stability of the competing CD8+ T-cell cognate ligand. When high affinity competitive CD8+ T cells were deleted by self-antigen expression, competition was abrogated. These findings show, for the first time to our knowledge, the existence of regulatory mechanisms that direct the responding CD8+ T-cell repertoire toward epitopes with high-stability interactions with MHC class I molecules. They also provide an insight into factors that facilitate CD8+ T-cell coexistence, with important implications for vaccine design and delivery.

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