HLA class I self peptides isolated from a T-cell leukemia reveal the allele-specific motif of HLA-B38.

ABSTRACT

Naturally-processed self peptides bound to HLA class I molecules of a T-cell leukemia (HLA-A1, A31, B38, B58) were isolated for sequence analysis. Acid-eluted peptides were subjected to reversed-phase HPLC separation and single-fraction sequencing was performed by Edman degradation. The peptides were found to be mostly nonamers and could be grouped into three distinct structural motifs. One of the peptide groups consistently displayed histidine at position 2 and a bulky hydrophobic residue at the C-terminus (XHXPXXXXY/F). The only HLA class I structure expressed by this T-cell leukemia which is consistent with the binding of peptides carrying this sequence motif is HLA-B38. A peptide binding assay confirmed this assignment. HLA-B38 is present in 10-12% of the Jewish population and is associated with several autoimmune disorders. The HLA-B38 motif may be an important tool for identifying potential T-cell epitopes involved in these diseases and for designing peptide vaccines.