Preferential expression of neo-CRP epitopes on the surface of human peripheral blood lymphocytes.

Antibodies specific for C-reactive protein (CRP) have been reported to react with certain human peripheral blood lymphocytes (PBL); however, the nature of the antigen has not been clearly defined. In the present study we identified the CRP antigenicity on PBL as a CRP neoepitope not seen on the native-CRP molecule. Neo-CRP epitopes are expressed when the native pentameric form of CRP is dissociated into free subunits. Commercial anti-CRP antisera were found to possess a significant proportion of specificities (up to 16% of the total reactivity) directed against neo-CRP antigenicity. Since similar reagents had been used in previous studies on the reactivity of anti-CRP antisera with PBL, we set out to determine if either native- or neo-CRP epitopes were preferentially expressed on PBL. We prepared antisera monospecific for native-CRP and neo-CRP, respectively, and characterized these reactivities in both direct and indirect enzyme immunoassays. When analyzed by flow cytometry, anti-neo-CRP but not anti-native-CRP antiserum was found to react with normal PBL. F(ab')2 fragments of affinity-purified anti-neo-CRP had identical activity, and the reactivity against CRP was absorbed by reagents expressing neo-CRP but not native-CRP epitopes. Flow cytometric analyses of monocyte-depleted PBL from 25 normal donors detected a mean of 23.8 +/- 5.8% anti-neo-CRP-positive cells, a higher proportion of PBL expressing the CRP antigen than previously reported. Our findings indicate that a molecule identical to, or cross-reactive with, a neo-antigenic form of CRP is present on the surface of a significant proportion of normal human PBL.