A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey.
Adaptive immunity in jawless vertebrates is mediated by leucine-rich repeat proteins called "variable lymphocyte receptors" (VLRs). Two types of VLR (A and B) are expressed by mutually exclusive lymphocyte populations in lamprey. VLRB lymphocytes resemble the B cells of jawed vertebrates; VLRA lymphocytes are similar to T cells. We determined the structure of a high-affinity VLRA isolated from lamprey immunized with hen egg white lysozyme (HEL) in unbound and antigen-bound forms. The VLRA-HEL complex demonstrates that certain VLRAs, like gammadelta T-cell receptors (TCRs) but unlike alphabeta TCRs, can recognize antigens directly, without a requirement for processing or antigen-presenting molecules. Thus, these VLRAs feature the nanomolar affinities of antibodies, the direct recognition of unprocessed antigens of both antibodies and gammadelta TCRs, and the exclusive expression on the lymphocyte surface that is unique to alphabeta and gammadelta TCRs.
Deng
Lu
L
W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA.
Velikovsky
C Alejandro
CA
Xu
Gang
G
Iyer
Lakshminarayan M
LM
Tasumi
Satoshi
S
Kerzic
Melissa C
MC
Flajnik
Martin F
MF
Aravind
L
L
Pancer
Zeev
Z
Mariuzza
Roy A
RA
D000818:Animals; D001665:Binding Sites; D002645:Chickens; D000939:Epitopes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D000090263:Leucine-Rich Repeat Proteins; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D048428:Petromyzon / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; D000090263:Leucine-Rich Repeat Proteins; D011506:Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C421864:hen egg lysozyme; D009113:Muramidase