Daa. Vignali et al., MINUTE QUANTITIES OF A SINGLE IMMUNODOMINANT FOREIGN EPITOPE ARE PRESENTED AS LARGE NESTED SETS BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES, European Journal of Immunology, 23(7), 1993, pp. 1602-1607
The processing and presentation of immunogenetic peptides is an obliga
te event in the generation of an immune response. However, the degree
of complexity with which an immunogenic foreign epitope is presented i
s still unclear. This question was addressed by analyzing the naturall
y processed peptides generated from exogenously-derived hen egg white
lysozyme (HEL) bound to the murine major histocompatibility complex (M
HC) class II molecule, H-2A(k). Using reversed-phase chromatography (R
PC), T cell hybridomas and mass spectrometry, 16 peptides were identif
ied that contain the minimal MHC binding epitope 52-61. These peptides
exhibited substantial N- and C-terminal extensions and ranged from 13
-28 amino acids in length. In contrast, MHC class I molecules present
peptides of 8-11 residues and each foreign epitope appears to be repre
sented by only a single peptide. The data here also show that only app
roximately 0.8% of the total bound peptide was derived from this singl
e HEL epitope. These findings provide direct evidence that relatively
small amounts of processed peptide are required to stimulate an effect
ive T cell response.