Antigen presentation of lysozyme: T-cell recognition of peptide and intact protein after priming with synthetic overlapping peptides comprising the entire protein chain.

Recently, using synthetic overlapping peptides which encompass the entire protein chain of hen egg lysozyme, the full submolecular profile of continuous regions on the protein recognized by T cells (T sites) was localized. In the present report, we have examined in two mouse strains the proliferative response to peptides and to native protein of lymph node cells from mice primed with synthetic overlapping peptides, either individually or as a mixture. It was found that the pattern of T-cell recognition observed after priming with peptides differs from that obtained when the native protein is used as the immunogen. Some, but not all, of the T-site containing peptides were effective in priming for an anti-lysozyme T-cell response. Several peptides which were highly immunogenic as free synthetic peptides were not associated with any of the known protein T sites. Further, some peptides were effective in priming for T cells that respond in vitro to the priming peptide, but not to the whole protein. If antigen processing proceeds via fragmentation, then only those regions containing T sites would be expected to be effective in priming for a T-cell response to the intact protein. Since this was not found to be the case, it is unlikely that fragmentation of lysozyme is a prerequisite for antigen presentation. Rather, we suggest that the critical aspects in the presentation of a protein antigen predominantly involve recognition of an intact protein, the interaction of which with the cell membrane triggers cellular activating events.