title: Alloantibody Generation and Effector Function Following Sensitization to Human Leukocyte Antigen.
abstract: Allorecognition is the activation of the adaptive immune system to foreign human leukocyte antigen (HLA) resulting in the generation of alloantibodies. Due to a high polymorphism, foreign HLA is recognized by the immune system following transplant, transfusion, or pregnancy resulting in the formation of the germinal center and the generation of long-lived alloantibody-producing memory B cells. Alloantibodies recognize antigenic epitopes displayed by the HLA molecule on the transplanted allograft and contribute to graft damage through multiple mechanisms, including (1) activation of the complement cascade resulting in the formation of the MAC complex and inflammatory anaphylatoxins, (2) transduction of intracellular signals leading to cytoskeletal rearrangement, growth, and proliferation of graft vasculature, and (3) immune cell infiltration into the allograft via FcγR interactions with the FC portion of the antibody. This review focuses on the generation of HLA alloantibody, routes of sensitization, alloantibody specificity, and mechanisms of antibody-mediated graft damage.
authors: Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, University of California Los Angeles , Los Angeles, CA , USA.
authors: Michelle J
authors: MJ
authors: Hickey
authors: Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, University of California Los Angeles , Los Angeles, CA , USA.
authors: Nicole M
authors: NM
authors: Valenzuela
authors: Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, University of California Los Angeles , Los Angeles, CA , USA.
authors: Elaine F
authors: EF
authors: Reed
keywords: Fc receptor; HLA antibody; allorecognition; complement; endothelium; human leukocyte antigen; non-HLA antibody; transplant