T-CELL RECOGNITION OF AN HLA-A2-RESTRICTED EPITOPE DERIVED FROM A CLEAVED SIGNAL SEQUENCE

An alternative pathway for class I-restricted antigen presentation has been suggested on the basis of peptides bound to HLA-A2 molecules in cells lacking the transporter for antigen presentation (TAP). Most of these peptides were derived from signal sequences for translocation in to the endoplasmic reticulum (ER). However, it is not known whether th ese peptides can be presented to T cells. The hydrophobic nature of an HLA-A2-restricted T cell epitope (M1 58-66) was exploited to test whe ther it could be presented to T cells when derived from a signal seque nce. Replacing the signal sequence of the influenza virus hemagglutini n molecule H3 with an artificial sequence containing that HLA-A2-restr icted T cell epitope resulted in efficient translocation of H3 molecul es into the ER and transport to the cell surface. This signal sequence -derived epitope was presented to HLA-A2-restricted T cells. Involveme nt of cytosolic processing for this presentation is very unlikely, bec ause (a) presentation occurred in cells lacking TAP; (b) expression of H3 molecules with the artificial signal sequence did not produce a de tectable cytosolic form of H3; and (c) presentation of the same epitop e expressed in cytosolic forms of antigen required TAP. Thus, a peptid e derived from a signal sequence cleaved in the ER can provide an epit ope for HLA-A2-restricted T cell recognition.