Abstract: | Using a primary limiting dilution approach to generate T cell lines, we compared myelin basic protein (MBP)-specific T cell clones from naive unprimed Lewis rat thymuses with the corresponding T cell repertoire of primed rats. We found that in the naive thymus repertoire MBP-specific, encephalitogenic T cell clones preferentially use T cell receptor Vβ8.2 genes, along with CDR3 sequences typical for the primed Lewis anti-MBP response. In contrast to T cells from primed immune organs, which all display the CD4+ CD8? phenotype, the majority of naive thymus-derived T cell clones expressed reduced levels of the CD4 co-receptor. Some clones were completely CD4?CD8?, while others included CD4? CD8? subpopulations along with CD4+CD8? T cells. In the one mixed population examined in detail, the CD4?CD8? and CD4+CD8? T cell subpopulations used a T cell receptor with identical β chain sequence. The data suggest that in the Lewis rat the biased T cell receptor gene usage by encephalitogenic T cells is a property of the natural thymic T cell repertoire, possibly as a consequence of positive selection. The unusually low expression of CD4 in the major histocompatibility complex class II-restricted autoreactive T cells could be related to their escape from negative selection within the thymus. |