Reactivity profiles of broadly neutralizing anti-HIV-1 antibodies are distinct from those of pathogenic autoantibodies

• DOI: 10.1097/qad.0b013e32834785cf
• Publication Date: 2011-04-20T07:10:01Z
• Authors: Harvir Singh; Kevin A Henry; Sampson ST Wu; Andrzej Chruscinski; Paul J Utz; Jamie K Scott
• Keywords: AIDS Vaccines; 0301 basic medicine; Enzyme-Linked Immunosorbent Assay; HIV Infections; HIV Antibodies; Antibodies, Neutralizing; Autoantigens; 3. Good health; Epitopes; 03 medical and health sciences; HIV-1; Humans; Autoantibodies

Broadly neutralizing antibodies (bNt Abs) against HIV-1 are rarely produced during natural infection, and efforts to induce such Abs by vaccination have been unsuccessful. Thus, elucidating the nature cellular origins of bNt is a high priority for vaccine research. As monoclonal (MAbs) 2F5, 4E10 2G12 reported bind select autoantigens, we investigated whether these MAbs display broader range autoreactivity how their compares with that pathogenic autoAbs.An autoantigen microarray comprising 106 connective tissue disease-related autoantigens control antigens was developed used, in combination ELISAs, compare reactivity profiles 4E10, 2F5 those four autoAbs derived from patients antiphospholipid-syndrome (APS), serum patient systemic lupus erythematosus (SLE).The APS SLE reacted strongly multiple on microarray, whereas anti-HIV-1 MAb limited mainly HIV-1-related antigens. The CL, yet only bound CL at concentrations; both epitopes 2-3-log higher apparent affinity than CL. Moreover, polyreactivity but not CL15, could be blocked dried milk.The fundamentally distinct arise dysregulated tolerance mechanisms. This suggests observed MAbs, HIV-1-Nt general, may through alternative mechanisms, as extensive somatic mutation due persistent antigen selection chronic infection.