HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cauerhff, A. Articles by Goldbaum, F. A. Search for Related Content PubMed PubMed Citation Articles by Cauerhff, A. Articles by Goldbaum, F. A.

Three-Dimensional Structure of the Fab from a Human IgM Cold Agglutinin¹

Ana Cauerhff^*, Bradford C. Braden, Julio Garcia Carvalho, Ricardo Aparicio, Igor Polikarpov, Juliana Leoni^* and Fernando A. Goldbaum^2,

^* Cátedra de Inmunología, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Facultad de Farmacia y Bioquímica UBA, Buenos Aires, Argentina; Department of Natural Sciences, Bowie State University, Bowie, MD 20715; Laboratório Nacional de Luz Síncrotron, Campinas, Brazil; and Instituto de Investigaciones Bioquímicas (Fundación Campomar, IIBBA-CONICET, FCEN-UBA), Buenos Aires, Argentina

Cold agglutinins (CAs) are IgM autoantibodies characterized by their ability to agglutinate in vitro RBC at low temperatures. These autoantibodies cause hemolytic anemia in patients with CA disease. Many diverse Ags are recognized by CAs, most frequently those belonging to the I/i system. These are oligosaccharides composed of repeated units of N-acetyllactosamine, expressed on RBC. The three-dimensional structure of the Fab of KAU, a human monoclonal IgM CA with anti-I activity, was determined. The KAU combining site shows an extended cavity and a neighboring pocket. Residues from the hypervariable loops V_HCDR3, V_LCDR1, and V_LCDR3 form the cavity, whereas the small pocket is defined essentially by residues from the hypervariable loops V_HCDR1 and V_HCDR2. This fact could explain the V_H4-34 germline gene restriction among CA. The KAU combining site topography is consistent with one that binds a polysaccharide. The combining site overall dimensions are 15 Å wide and 24 Å long. Conservation of key binding site residues among anti-I/i CAs indicates that this is a common feature of this family of autoantibodies. We also describe the first high resolution structure of the human IgM C_H1:C_L domain. The structural analysis shows that the C_H1-C_L interface is mainly conserved during the isotype switch process from IgM to IgG1.

This article has been cited by other articles:

				K. N. Potter, P. Hobby, S. Klijn, F. K. Stevenson, and B. J. Sutton Evidence for Involvement of a Hydrophobic Patch in Framework Region 1 of Human V4-34-Encoded Igs in Recognition of the Red Blood Cell I Antigen J. Immunol., October 1, 2002; 169(7): 3777 - 3782. [Abstract] [Full Text] [PDF]

				E. Meffre, M. Chiorazzi, and M. C. Nussenzweig Circulating Human B Cells That Express Surrogate Light Chains Display a Unique Antibody Repertoire J. Immunol., August 15, 2001; 167(4): 2151 - 2156. [Abstract] [Full Text] [PDF]