Marie-Hélène Côté

Syntagmatic distinctness in consonant deletion

This article examines the role of distinctness between adjacent segments in consonant deletion. On the basis of five stop-deletion patterns, it establishes a correlation between the likelihood of cluster simplification and the level of similarity between the consonants in the cluster. This correlation is motivated on perceptual grounds, and an OT analysis of similarity avoidance is provided in which perceptual factors are integrated in the grammar through both faithfulness and markedness constraints. This perceptual approach improves in two ways on previous analyses, notably the OCP. First, it integrates similarity avoidance within a more general perception-based framework, which accounts naturally for its gradient nature. Second, it uncovers a distinction between absolute and contextual similarity avoidance between adjacent segments, depending on whether similarity avoidance is established without reference to the context in which the segments appear or relative to the quality of the perceptual cues available to the segments.

Sorting of MHC class II molecules into exosomes through a ubiquitin-independent pathway.

Major histocompatibility complex class II (MHC‐II) molecules accumulate in exocytic vesicles, called exosomes, which are secreted by antigen presenting cells. These vesicles are released following the fusion of multivesicular bodies (MVBs) with the plasma membrane. The molecular mechanisms regulating cargo selection remain to be fully characterized. As ubiquitination of the MHC‐II β‐chain cytoplasmic tail has recently been demonstrated in various cell types, we sought to determine if this post‐translational modification is required for the incorporation of MHC‐II molecules into exosomes. First, we stably transfected HeLa cells with a chimeric HLA‐DR molecule in which the β‐chain cytoplasmic tail is replaced by ubiquitin. Western blot analysis did not indicate preferential shedding of these chimeric molecules into exosomes. Next, we forced the ubiquitination of MHC‐II in class II transactivator (CIITA)‐expressing HeLa and HEK293 cells by transfecting the MARCH8 E3 ubiquitin ligase. Despite the almost complete downregulation of MHC‐II from the plasma membrane, these molecules were not enriched in exosomes. Finally, site‐directed mutagenesis of all cytoplasmic lysine residues on HLA‐DR did not prevent inclusion into these vesicles. Taken together, these results demonstrate that ubiquitination of MHC‐II is not a prerequisite for incorporation into exosomes.

The nature of the schwa/zero alternation in French clitics: experimental and non-experimental evidence

This article examines the phonological status of schwa in clitics, in particular whether or not schwa should be included in their lexical representation. Several distributional and experimental arguments pointing to the lexical status of clitic schwas are reviewed and are shown to be inconclusive, due to the existence of additional data that suggest a different interpretation not involving underlying schwas. The discussion includes experimental results that fail to show residual lip rounding in the vicinity of an omitted schwa at clitic boundaries, contra Barnes and Kavitskayas (2002) previous claim. In the absence of evidence to the contrary, the non-contrastive nature of clitic schwas militates against their underlying status.

Consonant cluster simplification in Québec French

Abstract This paper investigates the process of word-final consonant cluster simplification in Québec French. Three categories of clusters are distinguished: (1) those that may be reduced in all lexical items (unrestricted simplification), (2) those that may be reduced in some lexical items but not in others (lexically-determined simplification), (3) those that are always stable. Consonant deletion is motivated by two distinct factors: the Sonority Sequencing Principle and a principle requiring that every segment be perceptually salient. The likelihood that a consonant deletes correlates with the degree to which it violates one of these principles. Appeal to perceptual factors explains in particular two tendencies. First, final stops are less susceptible to deletion than other consonants. Second, cluster simplification correlates with the amount of contrast within the cluster, in terms of voicing, manner and place of articulation. This analysis of cluster reduction supports the integration of perception in phonological theory advocated in a growing body of work. It is formalized within Optimality Theory and uses in particular perceptually-motivated markedness and faithfulness constraints militating against perceptually weak segments.

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

Adoptive transfer of autologous dendritic cells (DCs) loaded with tumor-associated CD4 and CD8 T cell epitopes represents a promising avenue for the immunotherapy of cancer. In an effort to increase the loading of therapeutic synthetic peptides on MHC II molecules, we used a mutant of HLA-DM (DMY) devoid of its lysosomal sorting motif and that accumulates at the cell surface. Transfection of DMY into HLA-DR+ cells resulted in increased loading of the exogenously supplied HA307–318 peptide, as well as increased stimulation of HA-specific T cells. Also, on transduction in mouse and human DCs, DMY increased loading of HEL48–61 and of the tumor Ag-derived gp100174–190 peptides, respectively. Interestingly, expression of DMY at the surface of APCs favored Th1 differentiation over Th2. Finally, we found that DMY− and DMY+ mouse APCs differentially stimulated T cell hybridomas sensitive to the fine conformation of peptide–MHC II complexes. Taken together, our results suggest that the overexpression of HLA-DMY at the plasma membrane of DCs may improve quantitatively, but also qualitatively, the presentation of CD4 T cell epitopes in cellular vaccine therapies for cancer.