The nature of the autoimmune antibody repertoire in human immunodeficiency virus type 1 infection.
Human immunodeficiency virus type 1 (HIV-1) seropositive donors typically have high serum antibody titers to a range of autoantigens, and the corresponding autoantibodies have been suggested to be of importance in the pathogenesis of HIV-1 infection. We have prepared 38 IgG human monoclonal autoantibodies from asymptomatic HIV-1 seropositive donors with elevated serum titers to autoantigens by construction of Fab combinatorial libraries on the surface of phage and affinity selection using a range of autoantigens, including double-stranded DNA, major histocompatibility complex class II, CD14, epidermal growth factor receptor, and ganglioside GD2. The autoantibodies are shown to be of moderate affinity and exhibit marked cross-reactivity with a range of antigens. This contrasts with the specific high-affinity antibodies selected (i) against infectious agents using the same libraries and (ii) against one of the autoantigens using a library from a donor with established autoimmune disease. The results lend no support to the presence of specific autoantibodies in HIV-1 infection and instead suggest attention should be focused on the pathological significance of high serum levels of antibodies capable of interacting with multiple molecular species.
Ditzel
H J
HJ
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Barbas
S M
SM
Barbas
C F
CF
Burton
D R
DR
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015723:Gene Library; D005803:Genes, Immunoglobulin; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D001323:Autoantibodies; D001324:Autoantigens; D017931:DNA Primers; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region