# T Cell Differentiation and Diversification in Jawless Vertebrates

> **NIH NIH R35** · EMORY UNIVERSITY · 2020 · $490,739

## Abstract

PROJECT SUMMARY
The proposed studies in lampreys and hagfish build on the findings that both jawless (agnathans) and jawed
(gnathostomes) vertebrates have prototypic T-like and B-like lymphocyte lineages, although jawless
vertebrates (lampreys and hagfish) generate variable lymphocyte receptors (VLR) for antigen recognition by
recombinatorial conversion of incomplete germline VLR genes (VLRA, VLRB and VLRC) into fully
assembled VLR genes using diverse leucine-rich-repeat (LRR) donor sequences. Analysis of the development,
distribution and function of the VLRA and VLRC lymphocyte lineages suggest that the VLRA and VLRC
lineages represent the agnathan T cell analogues of gnathostome α/β and γ/δ T cells with allorecognition
responsibility. The multistep assembly of VLRC and VLRA genes coincides with expression of cytidine
deaminase1 (CDA1) in a thymus-equivalent region of the gills, whereas VLRB and CDA2 expression occurs
primarily in hematopoietic tissues. Surprisingly, three additional CDA1-like genes, the products of which have
deaminase and mutagenic activity, have now been identified. The proposed studies will define the newly
discovered multigene CDA1 family members in agnathans, determine their cellular expression patterns and
elucidate the structure and functions of their protein products. Circumstantial evidence implies that the VLRA
and VLRC receptors rely on associated transmembrane molecules for their cell surface expression and
signaling competence. The present studies will determine the composite receptor structure and signaling
competence for VLRA and VLRC. Pilot studies indicate that the VLRA+ and VLRC+ lymphocytes preferentially
respond to allogeneic white blood cells. The antigens recognized by VLRA and VLRC receptors will be defined
with the related goal of identifying lamprey histocompatibility antigens and determining their roles in antigen
presentation. Candidate histocompatibility genes will be examined for genetic polymorphism, expression
patterns and immunostimulatory potential to test the hypothesis that VLRA and VLRC recognize
histocompatibility-associated antigens. Identification of the agnathan histocompatibility genes will enlighten us
about the mechanisms of self versus non-self discrimination at a pivotal juncture of vertebrate evolution.

## Key facts

- **NIH application ID:** 9897541
- **Project number:** 5R35GM122591-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Max Dale Cooper
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $490,739
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897541

## Citation

> US National Institutes of Health, RePORTER application 9897541, T Cell Differentiation and Diversification in Jawless Vertebrates (5R35GM122591-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897541. Licensed CC0.

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