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The Role of an Exposed Loop in the α 2 Domain in the Mouse MHC Class I H‐2D d Molecule for Recognition by the Monoclonal Antibody 34‐5‐8S and the NK‐Cell Receptor Ly49A
Author(s) -
Waldenström M.,
Achour A.,
Michaelsson J.,
Rölle A.,
Kärre K.
Publication year - 2002
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2002.01027.x
Subject(s) - major histocompatibility complex , monoclonal antibody , mutant , microbiology and biotechnology , epitope , mhc class i , receptor , transfection , biology , chemistry , antigen , antibody , biochemistry , genetics , gene
Natural killer (NK) cells express major histocompatibility complex (MHC) class I‐specific inhibitory receptors. The region mediating the protective effect of the MHC class I molecule H‐2D d (D d ), recognized by the inhibitory receptor Ly49A, has been mapped to the α 1 /α 2 domains. Here we have focused on an exposed loop in the N‐terminal part of the α 2 domain, which constitutes a major structural motif that differs between D d (strong binding to Ly49A) and D b (weak binding to Ly49A at best). We mutated the residues 103, 104 and 107 in D d to the corresponding amino acids in D b . The D d mutant molecule retained the ability to be stabilized by a D d ‐binding peptide. However, the mutation totally abolished the recognition by the conformational dependent monoclonal antibody (MoAb) 34‐5‐8S, known to inhibit the interaction between D d and Ly49A. In addition, there was a marked impairment of the binding to Ly49A as evaluated by the ability of tetramers of the D d mutant molecule to bind to Ly49A‐transfected reporter cells and spleen cells. These results demonstrate that the introduced changes at positions 103, 104 and 107 directly or indirectly affect the epitopes for the MoAb 34‐5‐8S and the Ly49A receptor.