A critical contemplation on the role of heat shock proteins in transfer of antigenic peptides during antigen presentation.
Evidence is presented to demonstrate that HSPs mediate transfer of antigenic peptides during antigen presentation by MHC class I-restricted T cells. Transfer of peptides through HSP-chaperones is preferred over direct diffusion of peptides to their destinations because of our belief that few molecular phenomena within cells occur in liquid-phase and there is little evidence for the presence of free peptides in the cell. Further, chaperoning of peptides by HSPs is likely to: (i) shield peptides from their ultimate degradation to single amino acids by cytosolic proteases, (ii) minimize the chances of fortuitous and unproductive coupling with other proteins, (iii) help achieve higher local peptide concentrations than might be possible by passive diffusion, and (iv) obtain a mechanism for the process of transfer to be regulated or modulated. The evidence in support of an involvement of HSPs in transfer of peptides is critically discussed. The theme that HSPs are functional fore-runners of the MHC molecules, first proposed by us (Srivastava and Heike, 1991), is further developed.
Li
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Department of Biological Sciences, Fordham University, Bronx, NY 10458.
Srivastava
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D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D008285:Major Histocompatibility Complex; D009369:Neoplasms / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases