Apoptotic U1-70 kd is antigenically distinct from the intact form of the U1-70-kd molecule.
OBJECTIVE
To determine whether immune responses to an apoptotically modified form of a human lupus autoantigen can be distinguished from immune responses to the intact form of the same antigen.


METHODS
Immunoblot and enzyme-linked immunosorbent assay techniques were used to test human autoimmune sera for the presence of antibodies to apoptotic forms of the U1- 70-kd small nuclear RNP antigen, while antibody recognition of intact U1-70 kd was blocked.


RESULTS
poptosis-specific U1-70-kd antibodies were identified by immunoblot in 15 of 29 sera with antibodies to intact U1-70 kd and in 2 of 25 sera without measurable antibodies to intact U1-70 kd. Bacterially produced, purified, caspase-cleaved U1-70 kd without additional posttranslational modifications was a target of apoptosis-specific antibodies in 3 of 9 U1-70-kd-positive sera tested.


CONCLUSIONS
The apoptotic form of U1-70 kd displays B cell epitopes that are not displayed on the intact form of U1-70 kd. Caspase cleavage in the absence of additional posttranslational modifications is sufficient to induce the display of some of these epitopes. Immunity to apoptotically modified proteins can develop against caspase-cleaved forms or against forms that undergo additional posttranslational modification.
Greidinger
Eric L
EL
University of Missouri and Department of Veterans Affairs Medical Research Service, Harry S Truman Memorial Veterans Hospital, Columbia, Missouri, USA. greidingere@health.missouri.edu
Foecking
Mark F
MF
Ranatunga
Sriya
S
Hoffman
Robert W
RW
D000918:Antibody Specificity; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D017412:Ribonucleoprotein, U1 Small Nuclear; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases