Development of HLA bound peptitides which have supressive activity.

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There are many diseases caused by abnormal immune responses. To develop the non stimulatory peptide analog that binds to HLA molecule, we investigated the HLA-peptide interactions. Interaction of HLA-DP9 (DPA1*0201/DPB1*0901) molecule and M protein of serotype 12 (SS95/12) streptococcus has been investigated. Seven antigenic peptides restricted by the HLA-DP9 molecule were identified. Comparison of the amino acid sequences among these peptides revealed HLA-DP9-specific binding motif, which differs from the binding motif to the HLA-DR molecules. In an analysis of T cell responses to synthetic peptides in mice transgenic for HLA-DR51 and -DQ6, we found that DR51 and DQ6 transgenic mice acquired significant T cell response to the peptides. This indicated that HLA transgenic mouse should be a useful tool to examine the function of HLA molecules in vivo. We also developed the DNA typing method using PCR/SSOP analysis for HLA-A,HLA-DR,DQ and DP alleles, and found several new alleles. Using this method we determined several susceptible genes for autoimmune disease.