HEAT-SHOCK PROTEINS IN IMMUNE-RESPONSE TO CANCER - THE 4TH PARADIGM

The involvement of heat shock proteins in immune response is categoriz ed into four distinct paradigms. In the First Paradigm, HSP derived fr om foreign organisms act as classical foreign antigens, and they elici t immune response to the non-conserved HSP epitopes. The Second Paradi gm refers to instances where the host responds to self HSP to which th ere is no central or peripheral tolerance. The Third Paradigm involves molecular mimicry, where cross-reactivity between an HSP and another protein leads to an immune response to the latter under conditions whi ch elicit an immune response to the former, such as infection with a b acterium whose immunodominant antigen is an HSP. The Fourth Paradigm r efers to situations where an HSP-antigen complex elicits an effective response to the antigen and not to the HSP. Thus the HSP acts as a car rier for the antigenic peptide. The role of HSP in recognition by gamm a delta T cells may also fall into this paradigm. In this article, the Fourth Paradigm is considered as a crucial element in the development of vaccines against cancers and infectious diseases, and is analyzed through the prism of the observed association of hsp70 species with an tigenic peptides.