Disease relevance of hsp

• Recent studies in nonobese diabetic mice have implicated the autoimmune destruction of pancreatic islet cells with immunity to a beta cell protein cross-reactive to Mycobacterium tuberculosis heat shock protein 65 (hsp 65) [1].
• In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95% [2].
• These hsp can stimulate potent T lymphocyte responses that may then contribute to cardiac damage associated with adriamycin therapy and picornavirus infections [3].
• EXPERIMENTAL DESIGN: To determine whether adriamycin and the picornaviruses stimulate hsp expression, cultured neonatal myocardial cells from BALB/c Cum mice were treated with heat-shock, adriamycin and either infectious or ultraviolet irradiated (noninfectious) CVB3 [3].
• Delayed-type hypersensitivity elicited by synthetic peptides complexed with Mycobacterium tuberculosis hsp 70 [4].

High impact information on hsp

• Established clones of mycobacteria-reactive gamma/delta+ T cells specifically recognized mycobacteria, but neither PPD nor hsp 65 [5].
• The islet cell 64,000-Mr autoantigen and hsp 65 proteins were physiologically and immunocompetitively distinct [1].
• From our analysis of arthritogenic T cell clone A2b, obtained from an arthritic Lewis rat and specific for the 180-188 epitope of mycobacterial 65-kDa heat-shock protein (hsp 65), the possible origin of AA was explained by the existence of a molecular mimicry of the 180-188 epitope with a cartilage-associated self antigen [6].
• In conclusion, the early inflammatory stages of arteriosclerotic lesions induced by immunization with hsp 65 can regress in the absence of additional risk factors for atherosclerosis, such as a cholesterol rich diet [7].
• RESULTS: Both adriamycin and infectious virus treatment of myocardial cells stimulated increased hsp expression [3].

Biological context of hsp

• Ultraviolet irradiation of the virus prevents virus replication and failed to elicit hsp production in heart cells [3].
• HLA-DR4-restricted T-cell epitopes from the mycobacterial 60,000 MW heat shock protein (hsp 60) do not map to the sequence homology regions with the human hsp 60 [8].
• These observations suggest that the epitopes from the mycobacterial hsp 60 presented to T cells in the context of HLA-DR4 could be relevant to autoimmunity [8].
• The amino acid sequence alignment of the PTB65K protein with the hsp-65K homologs revealed that the M. tuberculosis and M. leprae proteins each differed by 36 amino acid residues and that the M. avium 18 protein differed by 8 residues [9].
• In this context, we isolated and sequenced the hsp-65K-encoding gene from our M. paratuberculosis PTB65K genomic library [9].

Anatomical context of hsp

• Therefore, our studies examined serological immunity to islet cell hsp in humans with insulin-dependent diabetes (IDD) [1].
• In summary, human resistant cells to tuberculosis respond to different classes of antigens, including constitutive cell wall proteins, secreted antigens, and hsp [10].
• Removal of T gamma cells from peripheral blood lymphocytes resulted in significantly increased responses to PPD and to recombinant mycobacterial hsp 65 and hsp 70 antigens [11].
• Identification of a novel B-cell epitope of restricted specificity on the hsp 65-kDa protein of Mycobacterium tuberculosis [12].

Associations of hsp with chemical compounds

• The treated myocardial cell homogenates were subjected to polyacrylamide gel electrophoresis and Western blot analysis for 70 kilodalton hsp [3].

Analytical, diagnostic and therapeutic context of hsp

• However, the results from animal models as well as human studies suggest that the mycobacterial hsp 60 may induce T-cell-mediated autoimmune conditions [8].
• T-cell responses to hsp 70 were easily generated by immunization with the purified chaperone alone, either after primary or secondary immunization [13].

References