to bind not only whole proteins, but also peptides. The affinity and specificity of this interaction is typically low. It was shown, that at least some of the HSPs possess this ability, mainly hsp70, hsp90, gp96 and calreticulin, and their peptide-binding sites were identified. In the case of gp96 it is not clear whether it can bind peptides in vivo, although its peptide-binding site has been found. But gp96 immune function could be peptide-independent, because it is involved in proper folding of many immune receptors, like TLR or integrins. Apart from that, HSPs can stimulate immune receptors and are important in proper folding of proteins involved in pro-inflammatory signaling pathways. Antigen presentation HSPs are indispensable components of antigen presentation pathways - the classical ones and also cross-presentation and autophagy. MHCI presentation In the simplified view of this pathway HSPs are usually not mentioned: antigenic peptides are generated in proteasome, transported into ER through protein transporter TAP and loaded onto MHCI, which then goes through secretory pathway on plasma membrane. But HSPs play an important part in transfer of unfolded proteins to proteasome and generated peptides to MHCI. Hsp90 can associate with proteasome and take over generated peptides. Afterwards, it can associate with hsp70, which can take the peptide further to the TAP. After passing through TAP, an ER chaperons are getting important - calreticulin binds peptides and together with gp96 form peptide loading complex for MHCI. This handing over with peptides is important, because HSPs can shield hydrophobic residues in peptides which would be otherwise problematic in aquatic cytosol. Also simple diffusion of peptides would be too ineffective. MHCII presentation In MHCII presentation, HSPs are involved in clathrin-dependent endocytosis. Also when HSPs are extracellular, they can guide their associated peptides into MHCII pathway, although it is not known how they are distinguished from the cross-presented ones (see below). Autophagy HSPs are involved in classical macroautophagy, when protein aggregates are enclosed by double membrane and degraded afterwards. They are also involved in special type of autophagy called "chaperone-mediated autophagy", when they enable cytosolic proteins to get into lysosomes. Cross-presentation When HSPs are extracellular, they can bind to specific receptors on dendritic cells (DC) and promote cross-presentation of their carried peptides. The most important receptors in this case are scavenger receptors, mainly SRECI and LOX-1. CD91 scavenger receptor has been previously proposed as the common HSP receptor. But now its relevance is