Generating data for databases--the peptide repertoire of HLA molecules

Abstract

During the past few years, a huge amount of information about HLA-presented peptides has been compiled: several thousand naturally processed ligands of such cell surface receptors are already known. Nevertheless, our knowledge covers only a minute proportion of the total peptide repertoire. The overall amount of different peptides presented by one given HLA class I molecule lies between 1000 and 10000 individual sequences per cell. There is, however, no HLA molecule of which more than 100 ligands have been published so far. The situation is further complicated by the fact that different cells present different sets of peptides by the same HLA molecules, a feature that provides great hope for immunotherapy. We have been analysing HLA-presented peptides for many years for three reasons. First, the basic rules of peptide presentation (the 'peptide motifs') had to be established. Second, the listing of individual peptides presented by HLA molecules is steadily continuing, although a comprehensive catalogue of all possible HLA-presented peptides is utopical in our days. Third, quantitative differences in the presentation of individual HLA ligands provide information about the dynamic state of the host cells. Comprehensive information about HLA-presented peptides enables accurate epitope prediction and provides a basis for diagnostic assessment and therapeutic intervention.