Heat-shock protein 60: implications for pathogenesis of and protection against bacterial infections.
In this review we have focused on antigenic features of hsp 60 related to: its ubiquitous distribution in the biosphere; its extraordinary homology among various bacteria; its high conservation from prokaryotic to eukaryotic cells; and its abundant expression under stress situations occurring during infection. These unique features make hsp 60 an excellent candidate antigen relevant to protection and pathogenesis of bacterial infections and, perhaps in a broader sense, to surveillance and autoimmunity. We will briefly discuss these possibilities in the following. Acquired resistance. If we assume that bacterial organisms contain some thousand different proteins which all represent potential antigens, the frequency of T cells with specificity for mycobacterial hsp 60 appears surprisingly high. Although, during the course of infection, high levels of hsp may be induced in bacteria, mere abundance appears to be an important though insufficient explanation. In addition, constant boosting by similar hsp 60 cognates from various microbes with which humans come into contact may contribute to dominance. This could easily explain the occurrence of hsp 60-specific T cells in healthy individuals with no clinical history of mycobacterial infections. Involvement of more sophisticated mechanisms, such as the affinity of hsp to other proteins, cannot be excluded (Flynn et al. 1989). Yet dominance does not necessarily mean protection and definite proof that hsp are protective antigens is lacking. Perhaps the immune response against epitopes shared by various mycobacterial pathogens represents a first line of defence preceding a more specific immune response. Such broadly reactive antigens would not qualify as prime candidates for vaccine design. Immunesurveillance. T cells with specificity for epitopes shared by bacterial and human hsp 60 are readily demonstrable and stressed host cells are recognized by hsp 60-specific T cells. Such T lymphocytes are endowed with the capacity to identify host cells stressed by a variety of assaults such as inflammation, infection, trauma, or transformation. Although it has been claimed that hsp-reactive gamma/delta T cells are particularly destined for such surveillance functions (Born et al. 1990, Asarnow et al. 1988), alpha/beta T cells could also participate. Pathogenesis. The mechanisms causing pathogenesis should be similar to those underlying protection and surveillance. In the former case bacterial hsp would be responsible for both induction of immunity and expression of pathogenic reactions; in the latter case an immune response stimulated by conserved regions of bacterial hsp 60 would be converted against a host-derived cognate.(ABSTRACT TRUNCATED AT 400 WORDS)
Kaufmann
S H
SH
Department of Immunology, University of Ulm, FRG.
Schoel
B
B
van Embden
J D
JD
Koga
T
T
Wand-Württenberger
A
A
Munk
M E
ME
Steinhoff
U
U
D000595:Amino Acid Sequence; D000818:Animals; D001424:Bacterial Infections / Q000209:etiology / Q000517:prevention & control*; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D008969:Molecular Sequence Data
D006360:Heat-Shock Proteins