Sequence and diversity of T-cell receptor beta-chain V and J genes of the owl monkey Aotus nancymaae

The New World primate Aotus nancymaae is susceptible to infection with the human malaria parasite Plasmodium falciparum and has therefore been recomme nded by the World Health Organization as a model for the evaluation of mala ria vaccine candidates. Recently, we have shown that Aotus TCRVA genes and TCRJA segments exhibit a high degree of similarity to human counterparts. I n the present report we used reverse transcription polymerase chain reactio n to analyze the sequences of A. nancymaae TCR beta-chain gene rearrangemen ts. Alignment with human sequences and phylogenetic comparison identified 1 8 distinct Aotus TCRBV genes homologous to the human TCRBV gene families, 4 , 5, 6, 7, 9, 12, 15, 24, and 28. Multiple Aotus genes were found in the TC RBV4, 5, 6, and 7 families. Some of these TCRBV genes aligned best to the s ame human gene and thus do not seem to have separate human homologues. Amin o acid sequences of the Aotus TCRBV genes were 77 to 90% identical to their closest human counterparts. Ten distinct Aotus TCRBJ segments homologous t o the human segments J1-1, J1-2, J1-4, J1-5, J1-6, J2-1, J2-2, J2-3, J2-4, J2-5 were found. In some cases the amino acid sequences of Aotus and human TCRBJ segments were completely identical. A comparison of the proportion of synonymous and nonsynonymous substitutions in Aotus vs human beta-chain-en coding genes revealed a dominance of synonymous substitutions in TCRBJ segm ents and of nonsynonymous substitutions in TCRBV segments. Dominance of non synonymous substitutions was more pronounced in TCRBV CDR1 and CDR2 regions than in the framework regions. No evidence for the emergence of new TCRBJ segments or TCRBV families was found. These results confirm that the TCR re pertoire in primates is remarkably stable and support the concept of using Aotus monkeys as an infection model for the evaluation of future subunit va ccine candidates.