HSP Immune Responses and Lack of Self Tolerance

Besides their immunodominance as microbial antigens, under various circumstances HSP do elicit immune responses also when (over-)expressed as self antigens by cells or tissues. And this seems to be a peculiar feature of HSP, especially because in many cases immune responses to this self antigen are not associated with pathogenic autoimmunity. Evidently, healthy individuals have a broad repertoire of T and B cells with specificity for mammalian or self HSP. Self HSP specific immunity has been...

Magea1

MAGE-A1 is one of 12 CT gene products that have been identified in numerous tumor types. MAGE-A1 interacts with the SKIP adaptor protein and histone deacety-lases to effectively repress the transcriptional transactivation activity of Notch1-IC, which is involved in cell fate decisions (Laduron et al., 2004). As a transcriptional regulator MAGEA1 may play a significant role in tumorigenesis by altering gene expression patterns associated with a number of signaling pathways. The first MAGE-A1 MHC...

Infection

Infection of cells with a variety of microorganisms could result in cell death by apoptosis or necrosis (Fischetti, 2005 Gruenberg and van der Goot, 2006 Mathis et al., 2005 Thorne et al., 2005a Thorne et al., 2005b). Lytic viruses are known to induce necrotic cell death (Brinkmann and Schulz, 2006 O'Shea , 2005 O'Shea et al., 2005). Infection of SK29-Mel-1 with the lytic parvovirus H1 occurs in the absence of HLA class I or costimulatory molecule upregulation (Moehler et al., 2003). In...

Hsf1 Nurd Complex

Model for gene repression by the HSF1 MTA1 NuRD complex. In the ACTIVE state, DNA is in an open conformation due to recruitment of HATs and ATP dependent remodeling complexes SWI SNF , and RNA polymerase II is able to transcribe the sequence of the structural gene. HSF1 recruitment by, for instance exposure to heregulin brings associated MTA1 and HDACs to the promoter, which deacetylates histones, recruit nucleosomes and lead to a compacted chromatin conformation that contributes to...

HSP Release from Damaged and Necrotic Cells

Necrotic cells release their contents into the extracellular environment so it is not surprising that HSP can be released in this manner. As would be expected in an unregulated release of cellular contents a range of HSP are found in the extracellular matrix during and after necrosis Basu et al., 2000 Berwin et al., 2001 Saito et al., 2005 . Necrotic cells, but not apoptotic cells, release Hsp72, Hsp90, grp94, and calreticulin Basu et al., 2000 . The increased release of HSP from necrotic...