# Specificity of Intestinal Immunoglobulin A

> **NIH NIH U01** · UNIVERSITY OF CHICAGO · 2020 · $491,720

## Abstract

ABSTRACT
More than 80% of mammalian antibody-secreting cells reside in the intestinal mucosa and secrete antibodies
of the immunoglobulin A (IgA) isotype. IgA deficiency is common in humans and predisposes toward various
intestinal pathologies including inflammatory bowel disease, celiac disease, and allergy. However, despite
decades of research, the specificity of IgA remains elusive. IgA coats a fraction of the intestinal microbiota, yet
the identities of the bacteria targeted by IgA and the types of humoral responses involved remain unknown.
IgA may also target dietary antigens, but it is unclear whether most IgA is directed against dietary antigens,
commensal microbiota, or other intestinal antigens. Lastly, specific antigens recognized by homeostatic IgA
antibodies have not been described. Here we present extensive preliminary data characterizing the
commensal bacteria targeted by IgA using a novel method involving bacterial flow cytometry and 16S rRNA
gene sequencing, termed IgA-Seq. We further present a method for cloning and expression of recombinant
monoclonal antibodies from single intestinal IgA-producing cells and rapid characterization of their reactivity
against microbiota using IgA-Seq. Finally, we detail a plan for determining the antigenic targets of these
antibodies with the following specific aims: 1) To characterize the origin and frequency of commensal-specific
B cells; and 2) To determine the specificities of single IgA antibodies. These data will be integrated to develop
a working understanding of the commensal bacteria and specific bacterial and/or dietary antigens that drive
homeostatic IgA responses. An understanding of the specificity of IgA will clarify hypotheses regarding its
elusive function. Further, manipulation of the IgA response may represent a promising therapeutic approach to
various microbiota-associated pathologies including inflammatory bowel disease, celiac disease, obesity, and
diabetes, but cannot be achieved without a thorough understanding of its specificity. Lastly, our studies will
generate a large panel of monoclonal antibodies specific for commensal microbiota that may allow
manipulation and characterization of defined bacterial subsets in healthy or dysbiotic microbiota and may have
applications as research, diagnostic, or therapeutic tools.

## Key facts

- **NIH application ID:** 9932880
- **Project number:** 5U01AI125250-05
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** ALBERT S. BENDELAC
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $491,720
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932880

## Citation

> US National Institutes of Health, RePORTER application 9932880, Specificity of Intestinal Immunoglobulin A (5U01AI125250-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932880. Licensed CC0.

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