Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate
Matthew N. Alder1,
Igor B. Rogozin2,
Lakshminarayan M. Iyer2,
Galina V. Glazko3,
Max D. Cooper1 and
Zeev Pancer4*
1 Howard Hughes Medical Institute, Departments of Medicine, Microbiology, Pediatrics, and Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
2 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
3 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
4 Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA.
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Fig. 1. Lamprey VLR diversity and gene rearrangement intermediates. (A) VLR scheme: signal peptide (SP), LRRNT, first LRR1, variable LRRV, end LRRVe, CP, and LRRCT (see text). Germline VLR-encoded portions of LRRNT and LRRCT are hatched. (B) Germline VLR gene rearrangement intermediates. Examples of LRR modules inserted from flanking cassettes into the germline gene: extensions of the VLR gene 5' LRRNT (F.1 + R.1 amplicons); replacements and extensions of the VLR gene 5' LRRCT (F.1 + R.2); and extensions of the VLR gene 3 ' LRRCT (F.2 + R.3). Most insertions terminate with an incomplete LRR. Position of forward (F) and reverse (R) primers indicated; black, cDNA clones; red, genomic clones; red line in Int.36 indicates a 78-nucleotide noncoding DNA flanking the LRRVe. (C) 3D model of VLR diversity region. Positively selected solvent-exposed residues on the concave surface are represented by colored spheres: red, LRRNT; yellow, LRR1; blue, LRRV; white, LRRVe; green, ß strands; magenta,  helices.
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Fig. 2. Antigen recognition by lamprey VLR. Immune responses after weekly injections of anthrax spore coats at 4, 6, and 8 weeks. (A) Plasma VLR reactivity with B. anthracis spores compared with B. subtilis (control); plasma dilution 1:200. (B) Plasma VLR recognition of the spore coat protein BclA; two individuals per time point; control, plasma from 8-week stimulated larva reacted with unrelated protein.
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