title: Conformational dynamics of the beta2-microglobulin C terminal in the cell-membrane-anchored major histocompatibility complex type I.
abstract: We have recently described an anti-beta2-microglobulin (beta2-m) monoclonal antibody (mAb 14H3) capable of recognizing the epitope 92-99 of the protein in the monomeric native state as well as in the fibrillar polymeric state, but not in the major histocompatibility complex type I (MHCI) anchored to the cell membrane. In the present study, we investigated the molecular basis for the inaccessibility of the C-terminal end of beta2-m in the MHCI complex, and demonstrated that mAb 14H3 binds the soluble fraction of the MHCI complex with a Kd of 0.3 microM. An interaction between the complex and the membrane protects beta2-m from immunological recognition at the MHCI level. This protection from antibody recognition can be weakened by procedures such as heat shock or gamma irradiation that perturb the membrane structure and commit the cell to the apoptotic pathway. mAb 14H3 can recognize MHCI in a transient state that most likely precedes beta2-m shedding and may be proposed as a useful tool for dynamic analysis of MHCI conformational modifications.
authors.affiliation: Biotechnology Research Laboratory, IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Massa
authors.forename: P
authors.initials: P
authors.lastname: Mangione
authors.forename: P
authors.initials: P
authors.lastname: Pignatti
authors.forename: M
authors.initials: M
authors.lastname: Stoppini
authors.forename: G
authors.initials: G
authors.lastname: Zanotti
authors.forename: P
authors.initials: P
authors.lastname: Arcidiaco
authors.forename: G
authors.initials: G
authors.lastname: Merlini
authors.forename: G
authors.initials: G
authors.lastname: Ferri
authors.forename: V
authors.initials: V
authors.lastname: Bellotti
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D011487:Protein Conformation; D012995:Solubility; D001613:beta 2-Microglobulin / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin