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25 July 2007

Paper:  Mycobacterial heat shock proteins as vaccines - a model of facilitated antigen presentation

Heat shock proteins (hsps) are a highly conserved family of proteins, first recognized by their upregulated expression in response to host exposure to raised temperatures. Further study has revealed that they have numerous functions in the cell, primarily as chaperones mediating both the correct folding of nascent polypeptide chains and the dissolution of aggregated protein complexes. The energy requirement for this chaperone activity is provided by the ATPase activity found in most families of hsps and thus the peptide binding capacity is controlled by ATP hydrolysis. The structural consequence of this is that hsps isolated in situ are found complexed to chaperoned peptides (hspCs). Much previous work has implicated hsps in the immune response to pathogens and recent studies have shown that the interaction of hsps with antigen presenting cells, such as dendritic cells (DCs), mediates the integration of the innate and acquired immune responses. This central role for hspCs in immunity is facilitated by their dual function in both innate immunity, with the induction of cytokines and the maturation of DCs mediated by the hsp component, and acquired immunity, with the trafficking of antigens chaperoned in hspCs for antigen presentation by the mature DCs.

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21 April 2004

Paper:  BCG HspCs induce T-helper 1 responses and protect against live challenge

The need for an effective TB (tuberculosis) vaccine remains acute, with tuberculosis still one of the major killers worldwide and 3 million new infections annually. We report here on the immune responses elicited by HspCs (heat-shock protein-peptide complexes) isolated from BCG (Bacille Calmette-Guerin) vaccine. These HspCs elicit both the appropriate cellular and protective immune responses required to merit their further development as TB vaccine candidates.

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22 August 2001

Paper:  Stressed bacteria and TB vaccines

The re-emergence of TB as a public-health problem in industrialized countries and, in particular, the emergence of antibioticresistant strains of Mycobacterium tuberculosis, have focused attention on the development of more-effective vaccines for this major threat to global health

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31 July 1998

Paper:  Towards a unified theory of immunity dendritic cells, stress proteins and antigen capture

In less than a decade, the archetypal view that the immune system exists primarily to distinguish "self" from "non-self" has been replaced by the paradigm that the immune system functions primarily to distinguish dangerous from non-dangerous antigens. This change is in part due to the recent reassertion of the importance of so-called innate immunity, which consists of non-specific components of the immune system such as macrophages that are active prior to exposure to antigens (In contrast, so-called acquired immunity depends upon the generation of B and T lymphocytes that are produced after exposure to the antigens and are specific for the antigens). The paradigm shift is also due to the recent proposal of the "danger model" of the immune system, which provides a conceptual mechanism by which the immune system might distinguish dangerous from non-dangerous antigens.

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