Structure and function: heat shock proteins and adaptive immunity.
Heat shock proteins (HSPs) have been implicated in the stimulation and generation of both innate and adaptive immunity. The ability of HSPs to bind antigenic peptides and deliver them to APCs is the basis of the generation of peptide-specific T lymphocyte responses both in vitro and in vivo. The different HSP families are genetically and biochemically unrelated, and the structural basis of peptide binding and the dynamic models of ligand interaction are known only for some of the HSPs. We examine the contribution of HSP structure to its immunological functions and the potential "immunological repertoire" of HSPs as well as the use of biophysical techniques to quantify HSP-peptide interactions and optimize vaccine design. Although biochemical evidence for HSP-mediated endogenous processing of Ag has now emerged, the issue of whether HSP-peptide complexes act as physiological sources of Ag in cross-presentation is controversial. We assess the contribution of biochemical studies in this field.
Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, United Kingdom. bj10001@cam.ac.uk
Babak
B
Javid
Paul A
PA
MacAry
Paul J
PJ
Lehner
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D001693:Biological Transport, Active / Q000235:genetics / Q000276:immunology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D008024:Ligands; D018448:Models, Immunological; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D006360:Heat-Shock Proteins; D008024:Ligands; D010455:Peptides; D014612:Vaccines