title: The isolated major histocompatibility complex class I alpha3 domain binds beta2m and CD8alphaalpha dimers.
abstract: The MHC class I molecule plays a crucial role in cytotoxic lymphocyte function. The heavy chain of the MHC class I molecule can form many non-covalent interactions with other molecules on multiple domains and surfaces. We have generated an isolated alpha3 domain of a murine MHC class I molecule and evaluated the contribution of this domain to binding with the MHC class I light chain, beta2m, and CD8. The alpha3 domain binds beta2m at a thousand-fold higher concentration than the whole MHC, and binds CD8alphaalpha with a dependence on the alpha3 CD loop. Our results are relevant for models of MHC folding and CD8-MHC function. The study of individual domains of complex molecules is an important strategy for understanding their dynamic structure and function.
authors.affiliation: Division of Monoclonal Ab, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Whitman
authors.forename: J
authors.initials: J
authors.lastname: Strohmaier
authors.forename: K
authors.initials: K
authors.lastname: O'Boyle
authors.forename: J M
authors.initials: JM
authors.lastname: Tingem
authors.forename: Y
authors.initials: Y
authors.lastname: Wilkinson
authors.forename: J
authors.initials: J
authors.lastname: Goldstein
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Brorson
authors.forename: M
authors.initials: M
authors.lastname: Brunswick
authors.forename: S
authors.initials: S
authors.lastname: Kozlowski
mesh_terms: D001665:Binding Sites / Q000235:genetics; D016827:CD8 Antigens / Q000378:metabolism*; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D001613:beta 2-Microglobulin