title: Igs expressed by chronic lymphocytic leukemia B cells show limited binding-site structure variability.
abstract: Ag selection has been suggested to play a role in chronic lymphocytic leukemia (CLL) pathogenesis, but no large-scale analysis has been performed so far on the structure of the Ag-binding sites (ABSs) of leukemic cell Igs. We sequenced both H and L chain V(D)J rearrangements from 366 CLL patients and modeled their three-dimensional structures. The resulting ABS structures were clustered into a small number of discrete sets, each containing ABSs with similar shapes and physicochemical properties. This structural classification correlates well with other known prognostic factors such as Ig mutation status and recurrent (stereotyped) receptors, but it shows a better prognostic value, at least in the case of one structural cluster for which clinical data were available. These findings suggest, for the first time, to our knowledge, on the basis of a structural analysis of the Ab-binding sites, that selection by a finite quota of antigenic structures operates on most CLL cases, whether mutated or unmutated.
authors: Department of Physics, Sapienza University of Rome, 00185 Rome, Italy. paolo.marcatili@gmail.com
authors: Paolo
authors: P
authors: Marcatili
authors: Fabio
authors: F
authors: Ghiotto
authors: Claudya
authors: C
authors: Tenca
authors: Anna
authors: A
authors: Chailyan
authors: Andrea N
authors: AN
authors: Mazzarello
authors: Xiao-Jie
authors: XJ
authors: Yan
authors: Monica
authors: M
authors: Colombo
authors: Emilia
authors: E
authors: Albesiano
authors: Davide
authors: D
authors: Bagnara
authors: Giovanna
authors: G
authors: Cutrona
authors: Fortunato
authors: F
authors: Morabito
authors: Silvia
authors: S
authors: Bruno
authors: Manlio
authors: M
authors: Ferrarini
authors: Nicholas
authors: N
authors: Chiorazzi
authors: Anna
authors: A
authors: Tramontano
authors: Franco
authors: F
authors: Fais
mesh_terms: D000941:Antigens / Q000737:chemistry / Q000276:immunology; D001665:Binding Sites; D016000:Cluster Analysis; D015870:Gene Expression; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics* / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
chemical_list: D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell