Identification and characterization of the T cell receptor (TCR) repertoire of the cynomolgus macaque (Macaca Fascicularis)

Swati Jaiswal; Sarah K Nyquist; Shayla Boyce; Tasneem Jivanjee; Samira Ibrahim; Joshua D Bromley; G James Gatter; Hannah Gideon; Kush Patel; Sharie Keanne Ganchua; Bonnie Berger; Sarah M Fortune; JoAnne L Flynn; Alex K Shalek; Samuel M Behar

doi:10.1186/s12864-022-08867-0

Identification and characterization of the T cell receptor (TCR) repertoire of the cynomolgus macaque (Macaca Fascicularis)

BMC Genomics. 2022 Sep 12;23(1):647. doi: 10.1186/s12864-022-08867-0.

Authors

Swati Jaiswal¹, Sarah K Nyquist^{2

3

4

5

6

7}, Shayla Boyce¹, Tasneem Jivanjee^{2

3

4}, Samira Ibrahim^{2

3

4}, Joshua D Bromley^{2

3

4

8}, G James Gatter^{2

3

4}, Hannah Gideon⁹, Kush Patel⁹, Sharie Keanne Ganchua⁹, Bonnie Berger^{5

6}, Sarah M Fortune^{10

11}, JoAnne L Flynn⁹, Alex K Shalek^{2

3

4

10

11

12}, Samuel M Behar¹³

Affiliations

¹ Department of Microbiology and Physiological Systems, Universityof Massachusetts Chan Medical School, Worcester, MA, USA.
² Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁵ Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁶ Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁹ Department of Microbiology and Molecular Genetics and Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁰ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
¹² Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.
¹³ Department of Microbiology and Physiological Systems, Universityof Massachusetts Chan Medical School, Worcester, MA, USA. samuel.behar@umassmed.edu.

Abstract

Background: Cynomolgus macaque (Macaca fascicularis) is an attractive animal model for the study of human disease and is extensively used in biomedical research. Cynomolgus macaques share behavioral, physiological, and genomic traits with humans and recapitulate human disease manifestations not observed in other animal species. To improve the use of the cynomolgus macaque model to investigate immune responses, we defined and characterized the T cell receptor (TCR) repertoire.

Result: We identified and analyzed the alpha (TRA), beta (TRB), gamma (TRG), and delta (TRD) TCR loci of the cynomolgus macaque. The expressed repertoire was determined using 22 unique lung samples from Mycobacterium tuberculosis infected cynomolgus macaques by single cell RNA sequencing. Expressed TCR alpha (TRAV) and beta (TRBV) variable region genes were enriched and identified using gene specific primers, which allowed their functional status to be determined. Analysis of the primers used for cynomolgus macaque TCR variable region gene enrichment showed they could also be used to amplify rhesus macaque (M. mulatta) variable region genes.

Conclusion: The genomic organization of the cynomolgus macaque has great similarity with the rhesus macaque and they shared > 90% sequence similarity with the human TCR repertoire. The identification of the TCR repertoire facilitates analysis of T cell immunity in cynomolgus macaques.

Keywords: Cynomolgus macaque; Locus map; NHP; T cell receptor; Variable region genes.

MeSH terms

Animals
Genome*
Genomics
Humans
Macaca fascicularis / genetics
Macaca mulatta / genetics
Mycobacterium tuberculosis* / genetics

Abstract

MeSH terms

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