Identification of a third variable lymphocyte receptor in the lamprey

Area of Science:

• Immunology
• Evolutionary Biology
• Genetics

Background:

• Jawless vertebrates (lampreys, hagfish) possess unique antigen receptors called variable lymphocyte receptors (VLRs), unlike jawed vertebrates' T-cell and B-cell receptors.
• VLRs are generated through recombination of leucine-rich repeat modules and are expressed on lymphocyte-like cells (LLCs).
• Two VLR types, VLRA and VLRB, have been identified, expressed on LLCs analogous to T and B cells.

Purpose of the Study:

• To identify and characterize novel VLR types in jawless vertebrates.
• To investigate the diversity and expression patterns of newly discovered VLRs.
• To understand the evolutionary origins of adaptive immunity.

Main Methods:

• Sequencing of approximately 100 VLRC cDNA clones from lamprey.
• Analysis of C-terminal cap diversity and structural features of VLRC.
• Single-cell PCR to determine LLC populations expressing VLRC, VLRA, or VLRB.

Main Results:

• Identification of a third VLR type in lampreys, designated VLRC.
• VLRC exhibits high sequence diversity, indicating its capacity as an antigen receptor.
• VLRC possesses a C-terminal cap with limited diversity and distinct structural characteristics compared to VLRA and VLRB.
• Single-cell PCR revealed a unique LLC population expressing VLRC exclusively.

Conclusions:

• The discovery of VLRC expands the known repertoire of VLRs in jawless vertebrates.
• VLRC likely functions as an antigen receptor, contributing to the adaptive immune response in lampreys.
• The existence of VLRC-expressing LLCs suggests a specialized immune cell lineage within the innate-like adaptive immunity of jawless vertebrates.