Natural Human Antibodies Retrieved by Phage Display Libraries from Healthy Donors: Polyreactivity and Recognition of Human Immunodeficiency Virus Type 1 gp120 Epitopes

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Abstract
We have characterized the human natural antibody repertoire that contains antibodies recognizing the human immunodeficiency virus type 1 (HIV‐1) gp120. A panel of monovalent antigen‐binding fragments (Fab) selected from IgM and IgG isotype libraries generated from peripheral blood mononuclear cells (PBMC) of a healthy, HIV‐1 noninfected individual was analysed, reflecting that only IgM, but not IgG, Fab were able to recognize HIV‐1 gp120. The IgM Fab antibodies were not restricted to any particular heavy chain variable region (VH) germ line gene. However, the recognition of gp120 is associated to polyreactive antibodies and all display low‐affinity interaction. This correlates with the absence of any maturation process as somatic mutation or isotype switch as the nucleotide sequence analysis of the variable regions reveals they are expressed near to germline configuration. In addition, none of the antibodies showed any neutralizing activity on HIV‐1‐infected lymphocytes, reflecting that the natural anti‐gp120 repertoire is not sufficient to neutralize HIV infection.