Analysis of heavy and light chain sequences of conventional camelid antibodies from Camelus dromedarius and Camelus bactrianus species.
Camel antibodies have been widely investigated, but work has focused upon the unique heavy chain antibodies found across camelid species. These are homodimers, devoid of light chains and the first constant heavy chain domain. Camelid species also display conventional hetero-tetrameric antibodies with identical pairs of heavy and light chains; in Camelus dromedarius these constitute 25% of circulating antibodies. Few investigations have been made on this subset of antibodies and complete conventional camel IgG sequences have not been reported. Here we study the sequence diversity of functional variable and constant regions observed in 57 conventional heavy, 18 kappa and 35 lambda light chains of C. dromedarius and Camelus bactrianus. We detail sequences of the full kappa and lambda light chain, variable and CH1 region for IgG1a and IgG1b and the CH2 and CH3 region for IgG1a. The majority (60%) of IgG1 variable region sequences aligned with the human IgHV3 family (clan III) and had leader sequences beginning with MELG whereas the remaining sequences aligned with the IgHV4 (clan II) and had leader sequences beginning with MRLL. Distinct differences in CDR length were observed between the two; where CDR1 was typically 5 and 7 residues and CDR2 at 17 and 16 residues, respectively. CDR3 length of IgHV4 (range 11 to 20) was closer to that typical of VHH antibodies than that of IgHV3 (range 3 to 18 residues). Designed oligonucleotide primers have enabled identification of paired heavy and light chains of conventional camel antibodies from individual B cell clones.
Department of Structural Biology, UCB, Slough, UK.
Laura M
LM
Griffin
Department of Bioinformatics, UCB, Slough, UK.
James R
JR
Snowden
Department of Structural Biology, UCB, Slough, UK.
Alastair D G
AD
Lawson
Central Veterinary Research Laboratory, P.O. Box 597, Dubai, United Arab Emirates.
Ulrich
U
Wernery
Central Veterinary Research Laboratory, P.O. Box 597, Dubai, United Arab Emirates.
Jorg
J
Kinne
Department of Structural Biology, UCB, Slough, UK. Electronic address: terry.baker@ucb.com.
Terry S
TS
Baker
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002162:Camelus / Q000145:classification / Q000235:genetics / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D000906:Antibodies; D022801:Complementarity Determining Regions; D017931:DNA Primers; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains
CDR length; CH1 domain; Camel IgG1; Kappa; Lambda; VHH