TCR/BCR repertoire sequencing in the conjunctival associated lymphoid tissue from trachoma longitudinal studies
Wellcome Trust
Kilimanjaro Clinical Research Institute
The primary aim of this study is to use next generation sequencing to investigate the T and B cell receptor repertoire in the conjunctival tissue in those susceptible to repeated ocular infection with Ct and those resistant despite similar exposures.RNA samples selected from archived conjunctival swab samples from a 4-year longitudinal study of children with progressing trachomatous scarring and non-progressing will be used. Sequences will be aligned to their germline V-, D-, and J-genes and assigned according to the IMGT/GENE-DB reference directory. The average length of CDR3 regions, as well as the frequency of shared CDR3s will be compared. The usage of specific V genes, families and their frequency will also be compared. Initial analysis will be conducted on 25 progressors and 25 non-progressors at the final time points. Based on the results of the data obtained, a sufficient number of samples will be selected for further analysis from earlier timepoints in the cohort. The project has the potential to contribute toward the evaluation and progression of current and future human clinical trials of Ct vaccines.
2.1 Biological and endogenous factors