Disclosed are domain antibodies that monovalently bind CD28. Domain antibodies that are monovalent for binding of CD28 can inhibit CD28 activity. In one aspect, a domain antibody consists of or comprises a single immunoglobulin variable domain that specifically binds and antagonizes the activity of CD28, in an aspect, without substantially agonizing CD28 activity. In another aspect, the domain antibody is a human domain antibody. The disclosure further encompasses methods of antagonizing CD80 and/or CD86 interactions with CD28 in an individual and methods of treating diseases or disorders involving CD80 and/or CD86 interactions with CD28, the methods involving administering a domain antibody to the individual.本發明揭示單價結合CD28之域抗體。結合CD28之單價域抗體可抑制CD28活性。在一態樣中,域抗體由單一免疫球蛋白可變域組成或包含單一免疫球蛋白可變域,特異性結合CD28且拮抗CD28活性,在一態樣中,實質上不促進(agonizing)CD28活性。在另一態樣中,該域抗體為人類域抗體。本發明另外涵蓋拮抗個體中CD80及/或CD86與CD28相互作用的方法,及治療涉及CD80及/或CD86與CD28之相互作用的疾病或病症的方法,該等方法涉及向該個體投與域抗體。