OLIGOCLONALITY OF HUMAN INTESTINAL INTRAEPITHELIAL T-CELLS

T cells bearing the T cell receptor alpha/beta (TCR-alpha/beta) are the predominant lymphocyte population in the human intestinal epithelium. To examine if normal intestinal intraepithelial lymphocytes (IEL) have a TCR repertoire distinct from the TCR-alpha/beta-repertoire in peripheral blood lymphocytes (PBL), comparative analysis of relative V-beta-gene usage in IEL and PBL was performed by quantitative polymerase chain reaction. In each of the six individuals examined, one to three V-beta-families made up more than 40% of the total V-beta-transcripts detected in the IEL, whereas there was a more even distribution of V-beta-gene usage in the paired PBL. The predominant V-beta-families, especially V-beta-l, V-beta-2, V-beta-3, and V-beta-6, were frequently shared among IEL of different individuals. PCR cloning and sequence analysis of the predominant V-beta-6 family in two individuals revealed an identical V-D-J-C sequence in 13 of 21 clones obtained from one donor, and a different repeated sequence in 18 of 27 clones examined in the second donor. These data suggest that the V-beta-skewing in IEL is due to an oligoclonal T cell expansion and may reflect the response of the intestinal mucosal immune system to a restricted set of as yet undefined antigens present in the gut.