TY - JOUR
T1 - Igs Expressed by Chronic Lymphocytic Leukemia B Cells Show Limited Binding-Site Structure Variability
AU - Marcatili, P.
AU - Ghiotto, F.
AU - Tenca, C.
AU - Chailyan, A.
AU - Mazzarello, A. N.
AU - Yan, X.-J.
AU - Colombo, M.
AU - Albesiano, E.
AU - Bagnara, D.
AU - Cutrona, G.
AU - Morabito, F.
AU - Bruno, S.
AU - Ferrarini, M.
AU - Chiorazzi, N.
AU - Tramontano, A.
AU - Fais, F.
N1 - KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUK-I1-012-43
Acknowledgements: This work was supported by Associazione Italiana Ricerca sul Cancro (IG-10698 to F.F.; IG-10492 to M.F.); Compagnia di San Paolo (4824 SD/CV, 2007.2880 to F.F.); Fondazione Maria Piaggio Casarsa, Genova, Italy (to F.G.); the National Institutes of Health (Grant RO1 CA81554 to N.C.); and King Abdullah University of Science and Technology (Grant KUK-I1-012-43 to A.T.). M.C. has a fellowship from the Associazione Italiana Ricerca sul Cancro 5 per Mille.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.
PY - 2013/5/1
Y1 - 2013/5/1
N2 - 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. Copyright © 2013 by The American Association of Immunologists, Inc.
AB - 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. Copyright © 2013 by The American Association of Immunologists, Inc.
UR - http://hdl.handle.net/10754/598554
UR - http://www.jimmunol.org/lookup/doi/10.4049/jimmunol.1300321
UR - http://www.scopus.com/inward/record.url?scp=84878082007&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1300321
DO - 10.4049/jimmunol.1300321
M3 - Article
C2 - 23636053
SN - 0022-1767
VL - 190
SP - 5771
EP - 5778
JO - The Journal of Immunology
JF - The Journal of Immunology
IS - 11
ER -