We have recently demonstrated that the p38 and ERK1/2 MAP kinases play reciprocal roles in the control of CD1d-mediated antigen presentation. Although the use of specific inhibitors for these pathways clearly had an effect, the effects were not complete, leading to speculations that additional pathways were involved. Here, we show that inhibiting protein kinase C d (PKCd) substantially impairs antigen presentation by murine CD1d1 to NKT cells. This effect was accompanied by marked changes in the intracellular localization of CD1d. Expression of a dominant-negative mutant of PKCd in CD1d + cells resulted in nearly undetectable endogenous antigen presentation, substantially impaired CD1d recycling, a decrease in MAPK activation, and a decrease in the ability to present low (but not high) concentrations of a-galactosylceramide at the cell surface. These data strongly suggest that PKCd is a critical regulator of CD1d-mediated antigen presentation and is involved in multiple steps of the process.
Qualitative methods were used to analyze postintervention interviews with 11 participants and their legacy recipients as well as the created legacy projects. Direct content analysis was used to assess feedback from the interviews about benefits, barriers, and recommendations regarding abbreviated DT. The legacy projects were coded for expression of core values.ResultFindings suggest that abbreviated DT effectively promotes (1) self-expression, (2) connection with loved ones, (3) sense of purpose, and (4) continuity of self. Participants observed that leading the development of their legacy projects promoted independent reflection, autonomy, and opportunities for family interaction when reviewing and discussing the projects. Consistent with traditional DT, participants expressed "family" as the most common core value in their legacy projects. Expression of "autonomy" was also a notable finding.Significance of resultsAbbreviated DT reduces resource barriers to conducting traditional DT while promoting similar benefits for participants and recipients, making it a promising adaptation warranting further research. The importance that patients place on family and autonomy should be honored as much as possible by those caring for adults with advanced-stage cancer.
Summary The mouse CD1d1 glycoprotein is specialized in presenting lipid antigens to a novel class of T cells called natural killer T (NKT) cells. CD1d1 is predicted to contain five potential N‐linked glycosylation sites (asparagine residues at positions 25, 38, 60, 128, and 183). Glycosylation has been shown to invariably affect the molecular and functional properties of various glycoproteins, and in the current report it was found that a conservative change of the individual endogenous asparagine residues in CD1d1 to glutamine differentially affected its functional expression. Although the maturation rate of the glycosylation mutants was comparable to that of wild type, they differed in their relative levels of surface expression and in their ability to stimulate NKT cells. Mutating all five glycosylation residues resulted in the absence of detectable CD1d1 expression, with a concomitant lack of NKT cell activation. Therefore, these results demonstrate that glycosylation plays a significant role in the functional expression of CD1d1.
the effects of mutating the four potential N-linked glycosylation sites of human CD1d (Padarau et al., J Biol Chem 2006; 281:40369-78). This paper was inadvertently omitted from being cited in our revised manuscript. We thank the editors for allowing us to both cite and correct the omission.This reference should appear on page 278, after reference 31 on the eighth line from the bottom of the second column in the Discussion section. The corrected sentence appears below.They speculated that these chaperones may bind to different glycans of the CD1d heavy chains, 31,62 similar to binding to the influenza virus haemagglutinin. 59The full reference that should appear in the reference list for this paper as reference 62 on page 281 is printed below.
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