T-cell recognition and antigen presentation of lysozyme.

Abstract

Several years ago, this laboratory introduced a comprehensive strategy for the systematic localization of all the continuous sites on a protein that are involved in B- and T-cell recognition. The strategy depends on the synthesis of consecutive overlapping peptides that together account for the entire protein chain. Using this approach, the full submolecular profile of continuous regions on hen egg lysozyme recognized by T cells (T sites) were localized. Four major T-cell recognition sites, three of which were subject to individual genetic control, were localized in the six mouse strains examined. In addition to these four continuous T sites, T-cell recognition of lysozyme also involved the three previously defined discontinuous antibody binding sites as demonstrated with lysozyme-specific long-term T cell cultures. Contrary to a long held impression, T-cell recognition, therefore, is not restricted only to sequence features, but can also be directed to protein discontinuous surface areas of high conformational dependency. More recently, 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. 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.(ABSTRACT TRUNCATED AT 250 WORDS)