HIV-1 Envelope Recognition by Polyreactive and Cross-Reactive Intestinal B Cells

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Mucosal immune responses are crucial for controlling HIV-1 infection.
• Tissue-resident B cells in the gut recognize HIV-1 envelope glycoproteins and secrete antibodies.

Purpose of the Study:

• To characterize B cells sensing HIV-1 in the gut of infected individuals.
• To analyze the properties of monoclonal antibodies from intestinal B cells.

Main Methods:

• Probing monoclonal antibodies from single intestinal B cells.
• Testing antibody binding to recombinant HIV-1 gp140 trimers.
• Assessing antibody affinity, polyreactivity, and cross-reactivity with self-antigens.

Main Results:

• A significant fraction of mucosal B cell antibodies were polyreactive with low affinity to HIV-1 envelope glycoproteins (gp160/gp140), especially gp41.
• High-affinity gp140 antibodies lacked neutralizing, ADCC, and transcytosis-blocking activities.
• Intestinal HIV-1 gp41 antibodies targeting HR2 cluster II cross-reacted with p38α MAPK14 (MAPK14).

Conclusions:

• Physiologic polyreactivity of intestinal B cells and molecular mimicry-based self-reactivity of HIV-1 antibodies are distinct phenomena.
• These phenomena may impair or divert mucosal humoral immunity against HIV-1.