Molecular Mapping of Antigenic and Cytotoxic T Lymphocyte Recognition Determinants on the Major Histocompatibility Complex Class I Molecule Kb Using In Vitro Mutant Cell Lines

Abstract

MHC class I molecule plays a crucial role in the cell-mediated immune response by functioning as the recognition element for cytotoxic T lymphocyte (CTL) to discriminate self-antigens from foreign (nonself) antigens (1). Based on the previous extensive studies using a series of spontaneous in vivo mouse mutants expressing altered class I K^b molecules with multiple clustered amino acid substitutions, we had postulated that CTL interacts with the “recognition regions” formed by amino acid residues in the polypeptide stretches from residues 70 to 90 in the α1 domain and from 150 to 180 in the α2 domain (2). In the present study, using allogeneic anti-K^b CTL clones, K^b-specific monoclonal antibodies (MAbs) and a series of mutant cell lines expressing K^b molecules with single point mutations, we have identified some of the amino acid residues on the two polypeptide stretches that are important for the recognition of the K^b molecule by CTL and MAbs (3). While the MAbs recognized specific regions in either the α1 or α2 domain of the molecule, CTL appeared to simultaneously interact with specific amino acid residues on the recognition regions of the two domains.