Molecular and structural properties of three autoimmune IgG monoclonal antibodies to histone H2B.
In systemic autoimmune diseases such as lupus the immune system produces autoantibodies to nuclear antigens including DNA and histone molecules. In the present study, we describe three monoclonal IgG antibodies that have been obtained from lupus-prone MRL/lpr mice. These three antibodies react with the amino terminus of histone H2B, a region of the molecule that is accessible in chromatin. Using a series of overlapping H2B synthetic peptides and structural analogues, we have mapped the different epitopes recognized by these antibodies. We have also sequenced the combining sites (variable regions) of the antibodies and modeled their interactions with the corresponding epitopes. Overall, the data suggest that the mechanisms of interaction with antigen are different for each of the three antibodies, even though they all react with the amino-terminal domain of the histone H2B molecule. The results also suggest that the binding between these antibodies and histone H2B is different from that between most antibodies and conventional protein antigens since the heavy chain complementarity-determining region 3 appears to play only a limited role in the three antibodies tested. The study of the interaction between self-antigens and spontaneously occurring autoantibodies may help us elucidate the mechanisms driving the expansion of self-reactive lymphocytes.
Monestier
M
M
Department of Microbiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. marcm@astro.temple.edu
Decker
P
P
Briand
J P
JP
Gabriel
J L
JL
Muller
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics; D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry* / Q000235:genetics; D015551:Autoimmunity; D005803:Genes, Immunoglobulin; D006657:Histones / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D006657:Histones; D007074:Immunoglobulin G