New insights suggesting a possible role of a heat shock protein 70-kD family-related protein in antigen processing/presentation phenomenon in humans

Abstract

A possible role of the peptide binding protein (PBP) 72/74 in antigen processing and presentation has been recently suggested in mice. In order to evaluate a possible analogous role of a PBP72/74-related protein in humans, immunoelectron microscope investigations, functional studies, and immunofluorescence analyses were performed on normal human peripheral antigen-presenting cells. We demonstrated that the determinant recognized by antiheat shock protein (HSP) 72/73 monoclonal antibody (MoAb) is constitutively expressed on the cell surface of monocytes as well as of B cells. Moreover, the capability of monocytes to present a recall antigen to T cells was significantly decreased when preincubated with an anti-HSP72/73 MoAb. These data add further strength to a potential role of a protein related to human PBP72/74 homologue in antigen processing and/or presentation. Finally, the capability of anti-HSP72/73 MoAb to impair the ability of fixed monocytes to present a synthetic peptide demonstrates that cell surface- localized PBP72/74-related protein could play a role in antigen presentation.

Intranuclear targeted delivery of functional NF-kappa B by 70kDa heatshock protein

“…In addition, we saw limited cytoplasmic uptake by two monocytic cell lines, THP-1 and U937, but only after extended (6-24 h) incubation with high concentrations (100 μg/ml) of Hsp70-FITC (data not shown). The B cell-and monocyte-specific Hsp70 transport activity we describe is consistent with reports which propose a role for Hsp70 heat shock family members in antigen presentation (Vanbuskirk et al, 1989;Manara et al, 1993), as these cells are generally considered to function as antigen-presenting cells. The cell-type specificity and inducibility of cellular Hsp70 uptake may reflect differential expression of a required surface or nuclear receptor for the Hsp70 protein.…”

Heat shock protein 70 upregulation is related to HLA‐DR expression in bronchial asthma. Effects of inhaled glucocorticoids

“…Moreover, normal human resting antigen-presenting cells express a determinant that is part of the human PBP72/74 homologue on their cell surface. These data and the ability of an anti-hsp72/73 monoclonal antibodies to consistently inhibit the antigen-presenting/ accessory cell functions of human monocytes suggest that human PBP72/74 homologue plays an important role in antigen presentation in the human immune system [31].…”

“…It is expressed on the cell surface of B cells, as well as on macrophages in mice [53]. Also in humans, the majority of CD14 positive monocytes coexpress the determinant recognized by anti-hsp72/73 monoclonal antibody [31]. Moreover, normal human resting antigen-presenting cells express a determinant that is part of the human PBP72/74 homologue on their cell surface.…”

“…Several genes for hsp70 are mapped within the major histocompatibility complex [30]. It has been observed that resting APCs express a hsp70-related protein on their cell surface [31]. Recently, hsp70 upregulation was demonstrated to be present in patients with bronchial asthma [32].…”

The antagonism of interferon-gamma (IFN-γ) by heparin: examination of the blockade of class II MHC antigen and heat shock protein-70 expression

“…In addition to their maintenance of normal protein structure, heat shock proteins have been implicated in the development of certain immune responses, including the development of autoimmune diseases [22]. Indeed, it has been suggested that the 70-kD family may play a role in antigen processing and presentation [23].…”