PROBLEM TO BE SOLVED: To provide isolated anti human NKG2D monoclonal antibodies useful for therapeutic applications in humans.SOLUTION: The invention relates to isolated monoclonal antibodies or antigen-binding fragments thereof which bind to hNKG2D when added to hNKG2D-expressing NK or T cells to crosslink no more than two hNKG2D dimers. The invention also provides a method of producing the antibody or antigen-binding fragment thereof, which method comprises culturing host cells having a nucleic acid encoding the antibody or antigen-binding fragment thereof under suitable conditions and recovering the antibody or its antigen-binding fragment. Other antigen-binding molecules such as antibody fragments, antibody derivatives and multi-specific molecules can be designed and derived from such antibodies.【課題】ヒトにおける治療的使用に有用な、単離された抗ヒトNKG2Dモノクローナル抗体の提供。【解決手段】hNKG2D発現NK又はT細胞に添加されたとき、hNKG2Dに結合し、2つまでのhNKG2D二量体を架橋する、単離されたモノクローナル抗体又はその抗原結合断片、並びに該抗体又はその抗原結合断片をコードする核酸を含む宿主細胞を適切な条件下で培養し回収することによる前記抗体又は抗原結合断片の製造方法。また、このような抗体から、抗体断片、抗体誘導体、及び多選択性の分子といった他の抗原結合分子を設計又は誘導することができる。【選択図】図20A