ORGANIZATION, STRUCTURE AND SEQUENCE OF THE RAT TCR BETA GENOMIC LOCI
A. R. Iyengar, A. M. Waaga, Cordula Magee, David R. Beier, Chaker N. Adra, Charles B. Carpenter, Mohamed H. Sayegh · Transplantation · 1999
154 The extreme diversity in the biological structure of the TCR is generated by recombination of gene segments and subsequent nucleotide substitution events that result in the functional alpha and beta genes. Data from our laboratory on the characterization of allo-reactive T cell clones specific to a class-II MHC allopeptide in the context of self-MHC (indirect pathway) in a WF-LEW rat model of acute kidney graft rejection revealed that these clones express a restricted TCR V beta repertoire and were capable of transferring a delayed type hypersensitivity response in-vivo. To undertake detailed studies on the phenomenon and to develop markers for the different clones it is necessary to have a knowledge of the TCR germ-line genomic loci in the rat model. To accomplish this objective, we undertook genomic characterization of the rat TCR beta region including the V gene segments. Three segments of the C region of rat TCR beta locus have already been characterized from the laboratory of Gutman et al. (J Immunol. 1991). The position of critical motifs, such as the TCR beta enhancer, positional elements that determine developmental specificity, etc., however is yet unknown. Sub-cloning and sequencing efforts of the TCR beta locus including the V region were carried out. P1 genomic clones obtained by screening a rat P1 genomic library with primers corresponding to the C region and V beta 9.0 gene segment (expressed by the class II allopeptide specific T cell clone) were used in this study. We report the characterization of a 60 kb region which includes the completed TCR beta locus (C region). (Figure)FigureIn addition, the organization and position of the different V beta gene segments are described. Understanding the gene structure and genomic organization of the complete TCR locus is critical in understanding physiological determinants of allo-recognition.