The V ~ I T Cell Receptor Repertoire in Human Small Intestine and Colon

VS1 bearing T ceils comprise the major population of 3'/8 T cells in the human intestinal tract. To gain insight into mechanisms involved in the generation of these cells and the diversity of their repertoire, we have characterized the junctional sequences of V81 T cell receptor transcripts in the human small intestine and colon. Mucosal biopsies obtained from defined regions along the length of the small intestine or colon contained a high frequency of either one or a few identical in frame V81 sequences. Less abundant sequences were also detected repeatedly throughout the length of small intestine or colon. Moreover, the intestinal V61 repertoire in the small intestine and colon appeared compartmentalized and showed no overlap with the V81 repertoire in peripheral blood. Dominant V81 transcripts in each subject differed between the small intestine and colon, and the dominant transcripts within these sites differed among individuals. Analysis of small intestinal transcripts obtained at a 1-yr interval revealed that the V51 repertoire was stable over time. The fact that the majority of V81 transcripts, both dominant and rare, are distributed throughout a several meter length of the adult intestinal tract and are stable over time suggests they are not generated by an ongoing process of in situ VDJ gene rearrangement. Our results favor a model in which the repertoire of V81 T cells in the intestinal tract is shaped by positive selection in response to a limited array of ligands before the migration of V(51 cells throughout the small intestine or colon.