EVIDENCE SUPPORTING A ROLE FOR CATHEPSIN-B IN THE GENERATION OF T-CELL ANTIGENIC EPITOPES OF HUMAN GROWTH-HORMONE

The elucidation of the enzymatic processing mechanism associated with the formation of antigenic peptide fragments that combine with MHC class II molecules is fundamental to our understanding of the immune system. We have investigated a structurally well defined protein, recombinant human growth hormone (rhGH), as an antigen, and present data supporting the hypothesis that the enzyme cathepsin B can produce peptide fragments bearing T cell epitopes associated with lymphocyte proliferative response to hGH in Balb/c (H-2(d)haplotype) mice. Minimal T cell epitopes are not generated; rather the cathepsin cleavage sites flank the three antigenic peptide regions, amino acid residues 31 41, 81-100, and 166-181.