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

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.

New insights into the Germline Genes and CDR3 Repertoire of the TCRβ chain inChiroptera

“…The (37 family members) super-amplification events of the TRBV12 family in pale spear-nosed bats and the large variation in TRBV gene numbers (30 and 100) among Chiroptera have never been reported in mammals. Because previous studies of primates: humans, rhesus monkeys, and crab-eating monkeys( 29, 38, 39 ),carnivores: cats, dogs, ferrets ( 40-42 ) and three species of camels( 43 ), species of the same order differed very little in TRB loci both in terms of loci structure and number of germline genes. Phylogenetic analysis classified Chiroptera as a sister order to Carnivora, and Artiodactyla ( 44 ), and we found that the distribution of TRBV gene families in the 3 bat species was more similar to that of Artiodactyla, with random and huge duplications.…”

“…Surprisingly, massive gene duplication events of the TRBV12 family in P. discolor and considerable variation in TRBV gene numbers among Chiroptera have never been reported in mammals. In comparison, studies of primates( 31–33 ), carnivores( 34–36 ), and camels( 37 ), have shown minimal differences in TRB loci structure and the number of germline genes among species of the same orders. The distribution and evolutionary direction of TRBV gene families in the three bat species is similar to Artiodactyla, with random and massive replications.…”

New insights into the germline genes and CDR3 repertoire of the TCRβ chain in Chiroptera

“…Surprisingly, massive gene duplication events of the TRBV12 family in P. discolor and considerable variation in TRBV gene numbers among Chiroptera have never been reported in mammals. In comparison, studies of primates ( 31 – 33 ), carnivores ( 34 – 36 ), and camels ( 37 ) have shown minimal differences in TRB loci structure and the number of germline genes among species of the same orders. The distribution and evolutionary direction of TRBV gene families in the three bat species are similar to Artiodactyla, with random and massive replications.…”

High-dimensional single-cell analysis unveils distinct immune signatures of peripheral blood in patients with pancreatic ductal adenocarcinoma

“…TCR is highly diverse heterodimers consisting of α and β chains (αβ TCR) expressed by most T cells. The variable regions of TCR α and δ chains are encoded by multiple variable (V) and linked (J) genes, while TCR β and γ chains are encoded by diversity (D) genes ( 15 , 16 ). The V region of TCR (Vα and Vβ) has three hypervariable regions, complementary determination region 1 (CDR1), CDR2 and CDR3, among which CDR3 has the largest variation, which directly determines the specificity and diversity of TCR ( 17 ).…”