Search

Objective: Analysis of T-cell receptor (TCR) beta-chain gene expression in atherosclerotic lesions of human aorta., Methods: TCR diversity was studied using non-radioactive polymerase chain reaction for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the beta-chain third complementarity-determining region (CDR3). Samples represent a wide range of atheromatous histology, allowing evaluation of the T-cell repertoire at different stages of disease., Results: Diverse TCRBV family usage was observed in the majority of the samples, as the 25 different TCRBV products were detected at levels exceeding background. The data also showed that TCRBV transcripts expressed in the diseased aorta tissue displayed considerable size heterogeneity and no repetition of CDR3 nucleotide motifs., Conclusions: The early presence of T-lymphocytes in the atheromatous blood vessel has been interpreted as an indication of specific immunological reactions operating during the course of the atherosclerotic process. Although a T-cell infiltrate characterized by limited usage of TCRAV genes cannot be excluded the unrestricted usage of TCRBV genes argues against a local T-cell clonal expansion in atherogenesis.

Callithrix jacchus is an outbred New World primate characterized by a naturally occurring bone marrow chimerism, restricted polymorphism at many MHC loci, and unusual susceptibility to viral pathogens, adenocarcinoma, colitis, and, following immunization with myelin antigens, a demyelinating disease of the central nervous system closely resembling human multiple sclerosis. Here we characterize the TCRB repertoire in this species, representing the first such analysis in a New World monkey. Two TCRBC, 13 BJ, 2 BD, and 15 BV genes were identified. Overall, a high degree of similarity with human TCRBV-D-J-C gene sequences was observed, indicating a close phylogenetic relationship. Biased usage in favor of genes from the TCRBC1-BJ1 cluster was present in 77% of sequences, in contrast to preferential usage of BC2-BJ2 genes known to occur in humans and mice. Complementarity-determining region 3 averaged 10 amino acids in length and were diverse. Framework regions of TCRBV genes were extensively conserved. Phylogenetic analysis of TCRBV sequences from different species indicated that TCR genes are highly stable across primates. Thus, a diverse TCRB repertoire is generated in C. jacchus despite the limited polymorphism of class I MHC loci. Extensive homology to human TCR genes, natural chimerism, and susceptibility to inflammatory disorders are characteristics of C. jacchus that create a useful model system for the study of human autoimmunity.