Immune responses to protein antigens require the recognition by T lymp
hocytes of major histocompatibility complex (MHC) molecules associated
to peptides derived from that protein. The MHC molecules can be of cl
ass I and/or II, depending on the type of immune response developed. T
he peptides that associate to MHC class I and II are different in stru
cture and origin. Class I molecules generally bind 8-10 amino acid-lon
g peptides derived from endogenous antigens. Class II molecules bind t
o longer peptides (14 to 20 amino acids) derived from either endogenou
s or exogenous antigens. The intracellular sites of generation and bin
ding of these peptides to MHC class I and class II molecules are disti
nct, MHC class I-binding peptides are generated in the cytosol, transl
ocated through the ER membrane by specific TAP transporters; the bindi
ng to MHC class I occurs in the lumen of the ER MHC class II-binding p
eptides are generated and bind class II molecules in the endocytic pat
hway. Recently, several groups identified and characterized a speciali
zed endocytic compartment, where MHC class II encounters and binds ant
igenic peptides.