ANCHOR RESIDUE MOTIFS OF HLA CLASS-I-BINDING PEPTIDES ANALYZED BY THEDIRECT BINDING OF SYNTHETIC PEPTIDES TO HLA CLASS-I ALPHA-CHAINS

The binding characteristics of the primary anchor residue motifs repor ted for HLA-A2 (A()0201, A(*)0205) and HLA-B27 (B(*)2705) alleles wer e investigated by a direct binding assay of the pertinent synthetic pe ptides to HLA class I alpha chains derived from a panel of HLA homozyg ous B-cell lines of various HLA phenotypes, including four A2 subtypes . The assay is based on a serologic detection of the conformational ch ange of HLA class I alpha chains induced by binding to specific peptid es in the presence of beta(2)m. It is applicable to test a large numbe r of HLA allelic products and synthetic peptides. Assay data confirmed the high allele specificity of the anchor residue motifs tested, but also revealed the intra- and interlocus cross-reactivity of these moti fs. In the case of A2 anchor motifs, not only a broad cross-reactivity within the A2 subgroup, but also cross-reactivities with A24, A26, A2 8, and A29 were observed. With B27 anchor motifs, an interlocus cross- reactivity with A3 and A31 was seen. Several peptides, even though the y carried A2 or B27 major anchor residue motifs, failed to bind to the relevant alpha chains, suggesting that the presence of a primary anch or residue motif is necessary for HLA class-I-peptide binding but is n ot by itself sufficient to guarantee binding.