ALLELE-SPECIFIC B-POCKET TRANSPLANT IN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX PROTEIN-CHANGES REQUIREMENT FOR ANCHOR RESIDUE AT P2 OF PEPTIDE

To investigate the role of an anchoring pocket in allele-specific pept ide presentation by a major histocompatibility complex class I molecul e, we ''transplanted'' a B pocket from HLA-A0201 into HLA-B*2705 by s ite-directed mutagenesis. The resulting protein, designated B27.A2B, b inds a different set of endogenous peptides than B2705 as evidenced b y complete loss of allorecognition as well as restored expression in t he antigen processing-defective mutant cell line T2. B27.A2B also fail s to present an HLA-B27-restricted influenza virus peptide [nucleoprot ein (383-391)] to cytotoxic T lymphocytes (CTLs). However, substitutio n of leucine, the predominant P2 anchor residue in A0201-restricted p eptides, for arginine, the P2 anchor in nucleoprotein-(383-391) and ot her B2705-restricted peptides, restores recognition of B27.A2B by the same B2705-restricted peptide-specific CTLs. These results demonstra te that a dominant polymorphic pocket in a class I molecule, through i nteraction with the anchor residue of an antigenic peptide, can distin guish among peptides differing by only a single amino acid and thus de termine the allelic specificity of peptide presentation.