Surface expression by mononuclear phagocytes of an epitope shared with mycobacterial heat shock protein 60

Abstract

Bone marrow-derived macrophages were stained with a variety of monoclonal antibodies (mAb) with specificity for the mycobacterial heat shock protein (hsp) 60 or with specific rabbit antiserum raised against mycobacterial hsp 60. The mAb ML30 as well as the specific antiserum brightly stained bone marrow-derived macrophages whereas all the other mAb as well as normal rabbit antiserum gave no or negligible reactivity. Surface expression of the shared epitope is observed by day 3 of in vitro cultivation and markedly increased by interferon-gamma stimulation on day 9. Although hsp 60 is thought to be restricted to the mitochondrial compartment, antibody responses to this molecule have been implicated in autoimmunity. Our finding that bone marrow-derived macrophages express a cross-reactive epitope recognized by an mAb with specificity for amino acids 275 to 295 of the mycobacterial hsp 60 is consistent with such a role.

Cutting Edge: Heat Shock Protein 60 Is a Putative Endogenous Ligand of the Toll-Like Receptor-4 Complex

“…The data represent means Ϯ SD of three to four experiments performed in quadruplicate. Significant differences to C3H/HeN (and C57BL/6) macrophages are indicated as ‫,ءءء‬ p Ͻ 0.001. response to diverse types of stress (3,4). We therefore have proposed that autologous hsp60 may serve as danger Ag to the innate immune system (2).…”

“…R ecent studies have suggested that autologous heat shock protein 60 (hsp60) 3 serves as a danger signal to the innate immune system. Mouse or human macrophages, as well as endothelial or smooth muscle cells, were found to elicit a proinflammatory response when incubated with recombinant human hsp60 (1,2).…”

“…These two cytokines are essential in driving the Th1 response. Since autologous hsp60 may be aberrantly expressed on the cell surface in response to stress (3,4) and will be set free from the cell interior during necrosis, these findings point to a role of hsp60 in initiating or sustaining Th1-dependent tissue inflammation (2). Interestingly, microbial hsp60/65 also induces a proinflammatory response in innate immune cells (5)(6)(7), suggesting that damaged autologous cells and microbial pathogens may alert innate immunity via the same recognition system.…”

Identification of atherosclerosis-associated conformational heat shock protein 60 epitopes by phage display and structural alignment

“…It is known, that HSP60, or at least parts of it, may be exposed on the cell surface [4][5][6]. Consequently, the next steps are to confirm the presence of this epitope within early atherosclerotic lesions and whether immune reactions against this epitope are involved in pathogenesis of atherosclerosis.…”

“…Since microbial HSP60s serve as major antigens in protection from, and pathogenesis of infectious diseases, autoimmune disorders such as rheumatoid arthritis, systemic sclerosis, psoriasis, Kawasaki's disease or Behcet's disease, are thought to be triggered by shared B-and T-cell epitopes cross-reactive between eukaryotic and prokaryotic HSP60 [3]. Interestingly, HSP60, which is physiologically active inside mitochondria, was found also on the surface of stressed eukaryotic cells, where it may serve as a danger signal and as target-(auto)-antigen for immune reaction [4][5][6].…”