1dl7: Difference between revisions

Revision as of 13:17, 21 February 2008

THE STRUCTURAL BASIS OF REPERTOIRE SHIFT IN AN IMMUNE RESPONSE TO PHOSPHOCHOLINE

OverviewOverview

The immune response to phosphocholine (PC)-protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC-protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC-protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC-phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65-NPPC complex at 2.35-A resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.

About this StructureAbout this Structure

1DL7 is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

The structural basis of repertoire shift in an immune response to phosphocholine., Brown M, Schumacher MA, Wiens GD, Brennan RG, Rittenberg MB, J Exp Med. 2000 Jun 19;191(12):2101-12. PMID:10859335

Page seeded by OCA on Thu Feb 21 12:17:43 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1dl7.gif|left|200px]]<br />
+[[Image:1dl7.gif|left|200px]]<br /><applet load="1dl7" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1dl7" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1dl7, resolution 2.35&Aring;" />
 '''THE STRUCTURAL BASIS OF REPERTOIRE SHIFT IN AN IMMUNE RESPONSE TO PHOSPHOCHOLINE'''<br />
 ==Overview==
-The immune response to phosphocholine (PC)-protein is characterized by a, shift in antibody repertoire as the response progresses. This change in, expressed gene combinations is accompanied by a shift in fine specificity, toward the carrier, resulting in high affinity to PC-protein. The, somatically mutated memory hybridoma, M3C65, possesses high affinity for, PC-protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine, (NPPC). Affinity measurements using related PC-phenyl analogues, including, peptides of varying lengths, demonstrate that carrier determinants, contribute to binding affinity and that somatic mutations alter this, recognition. The crystal structure of an M3C65-NPPC complex at 2.35-A, resolution allows evaluation of the three light chain mutations that, confer high-affinity binding to NPPC. Only one of the mutations involves a, contact residue, whereas the other two have indirect effects on the shape, of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural, evidence for the role of carrier determinants in promoting repertoire, shift. These two antibodies express unrelated variable region heavy and, light chain genes and represent a classic example of the effect of, repertoire shift on maturation of the immune response.
+The immune response to phosphocholine (PC)-protein is characterized by a shift in antibody repertoire as the response progresses. This change in expressed gene combinations is accompanied by a shift in fine specificity toward the carrier, resulting in high affinity to PC-protein. The somatically mutated memory hybridoma, M3C65, possesses high affinity for PC-protein and the phenyl-hapten analogue, p-nitrophenyl phosphocholine (NPPC). Affinity measurements using related PC-phenyl analogues, including peptides of varying lengths, demonstrate that carrier determinants contribute to binding affinity and that somatic mutations alter this recognition. The crystal structure of an M3C65-NPPC complex at 2.35-A resolution allows evaluation of the three light chain mutations that confer high-affinity binding to NPPC. Only one of the mutations involves a contact residue, whereas the other two have indirect effects on the shape of the combining site. Comparison of the M3C65 structure to that of T15, an antibody dominating the primary response, provides clear structural evidence for the role of carrier determinants in promoting repertoire shift. These two antibodies express unrelated variable region heavy and light chain genes and represent a classic example of the effect of repertoire shift on maturation of the immune response.
 ==About this Structure==
-DL7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NCH as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1DL7 OCA].
+DL7 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NCH:'>NCH</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DL7 OCA].
 ==Reference==
@@ Line 20: / Line 19: @@
 [[Category: single chain fv]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 09:28:29 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:17:43 2008''