This application provides, inter alia, antibodies or antigen-binding fragments thereof, targeting CTLA-4 expressed on injured tissues associated with multiple diseases. These anti-CTLA-4 antibodies, or antigen-binding fragments thereof, have a high affinity for CTLA-4 and function to inhibit CTLA-4. The antibodies and antigen-binding fragments are useful for treatment of human diseases, infections, and other conditions.