THE IMMUNODOMINANT REGION OF STAPHYLOCOCCAL NUCLEASE IS REPRESENTED BY MULTIPLE PEPTIDE SPECIES

Several published reports have lead to the characterization of natural ly processed peptides that are presented in association with either cl ass I or class II MHC molecules. Most peptides isolated from class II molecules are heterogeneous in length and exhibit ragged amino and car boxy termini. An intriguing finding was that one region of a molecule was often represented by many distinct peptides, rather than by a sing le dominant peptide species. Each of the peptides representing this do minant region exhibited a common core of amino acids, suggesting that this core may play a significiant role in the binding of the peptide t o class II and the recognition by peptide-specific T cells. Work from our laboratory has focused on the mechanisms involved in the immunodom inance of antigenic determinants using the bacterial antigen Staphyloc occal nuclease (Nase) as a model. Using truncated synthetic peptides, we have identified the immunodominant determinant of Nase to be locate d within the region 81-100 with a minimal antigenic core of 91-100 as determined. Addition of five residues to the carboxy terminus of this peptide had a negative effect on T cell recognition of this region, Th e present studies were undertaken in an effort to determine the sequen ce of the naturally processed immunodominant Nase determinant(s) prese nted in association with I-E(k) class II. Our results indicate that th e dominant region of the Nase molecule is represented by at least four distinct peptide species that are predicted to lie between residues 8 6 and 106 with a common core sequence of 91-96. These results indicate that the negative effects of flanking regions are dependent upon leng th and amino acid composition, and thus the use of truncated peptides to study minimal antigenic determinants may be misleading. (C) 1996 Ac ademic Press, Inc.