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Comprehensive analysis and characterization of the TCR α chain sequences in the common marmoset

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Abstract

The common marmoset (Callithrix jacchus) is useful as a nonhuman primate model of human diseases. Although the marmoset model has great potential for studying autoimmune diseases and immune responses against pathogens, little information is available regarding the genes involved in adaptive immunity. Here, we identified one TCR α constant (TRAC), 46 TRAJ (joining), and 35 TRAV (variable) segments from marmoset cDNA. Marmoset TRAC, TRAJ, and TRAV shared 80%, 68–100%, and 79–98% identity with their human counterparts at the amino acid level, respectively. The amino acid sequences were less conserved in TRAC than in TCRβ chain constant (TRBC). Comparative analysis of TRAV between marmosets and humans showed that the rates of synonymous substitutions per site (d S ) were not significantly different between the framework regions (FRs) and complementarity determining regions (CDRs), whereas the rates of nonsynonymous substitutions per site (d N ) were significantly lower in the FRs than in CDRs. Interestingly, the d N values of the CDRs were greater for TRBV than TRAV. These results suggested that after the divergence of Catarrhini from Platyrrhini, amino acid substitutions were decreased in the FRs by purifying selection and occurred more frequently in CDRβ than in CDRα by positive selection, probably depending on structural and functional constraints. This study provides not only useful information facilitating the investigation of adaptive immunity using the marmoset model but also new insight into the molecular evolution of the TCR heterodimer in primate species.

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Acknowledgments

This work was in part supported by Grants-in-Aids for Research on Emerging and Re-emerging Infectious Diseases by the Ministry of Health, Labor and Welfare, Japan (grant H20-shinkou-ippan-015) and Research on Publicly Essential Drug and Medical Devices from the Japan Health Sciences Foundation (grants KH53333 and KHC3332).

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Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, 18-1 Sakuradai, Sagamihara, Kanagawa, 228-0815, Japan

    Yoshiki Fujii, Kazutaka Kitaura & Ryuji Suzuki

  2. Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan

    Yoshiki Fujii, Kazutaka Kitaura, Tomohiko Takasaki & Ichiro Kurane

  3. Division of Immunology and Embryology, Department of Cell Biology, Tohoku University School of Medicine, Sendai, Japan

    Takaji Matsutani & Tsunetoshi Itoh

  4. Section of Biological Science, Research Center for Odontology, Nippon Dental University School of Life Dentistry, Tokyo, Japan

    Satsuki Suzuki

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  1. Yoshiki Fujii
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  2. Takaji Matsutani
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  3. Kazutaka Kitaura
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  4. Satsuki Suzuki
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  7. Ryuji Suzuki
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  8. Ichiro Kurane
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Correspondence to Ryuji Suzuki.

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Supplemental Table 1

Comparison of rates of synonymous (dS) or nonsynonymous substitutions per site (dN) in FRs and CDRs of TRBV between humans and the Rhesus monkeys (Macaca mulatta). (DOC 76 kb)

Supplemental Figure 1

Total RNA was separately extracted from seven individual common marmosets (nos. 1–7). PCR amplification was performed with either TRAV8-6s1 (s1) or TRAV8-6s2 (s2) and CjCA3 primer. The cDNA clones encoding TRAV8-6s1 or TRAV8-6s2 segment were used as positive control. (DOC 1056 kb)

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Fujii, Y., Matsutani, T., Kitaura, K. et al. Comprehensive analysis and characterization of the TCR α chain sequences in the common marmoset. Immunogenetics 62, 383–395 (2010). https://doi.org/10.1007/s00251-010-0445-0

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