Abstract
Motifs for peptides which bind specifically to the human class I major histompatibity complex molecules HLA-A2 and B7 were determined by sequence analysis of class I-bound peptides selected from a random synthetic library of nonamers. Thirteen individual peptides were sequenced for HLA-AZ, twelve individual and nine pooled peptides were sequenced for HLA-B7. Analysis of sequence alignment implicated four peptide positions in potential contact with the class I HLA-A2 molecule and three positions for the HLA-B7 molecule. The results demonstrate that a synthetic peptide library can be used to identify allele-specific motifs for class I molecules, providing information comparable to the results obtained from sequencing endogenous peptides. This method utilizes denatured class I heavy chains, and similar results were obtained using a class I protein purified from ma~alian cells or by expression in Escherichia coii. This method has the potential to detect peptides which may not be generated physiolo~cally, but due to their binding properties, may be valuable to predict or engineer immunomodulatory T cell epitopes.
The results demonstrate that a synthetic peptide library can be used to identify allele-specific motifs for class I molecules, providing information comparable to the results obtained from sequencing endogenous peptides.