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A Particular TCR Variable Region Used by T Cells Infiltrating Kidney Transplants¹

Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02129

Immune tolerance to MHC class II identical renal grafts is achievable in miniature swine following a short immunosuppressive treatment. Like in clinical transplants, swine-accepted allografts are primarily infiltrated by CD8⁺ T cells, which are noncytotoxic to the renal tissue. However, the actual specificity and function of these intragraft-infiltrating lymphocytes remain poorly understood. To develop the molecular tools to study TCR-associated functions of graft-infiltrating cells in a preclinical transplantation model, we have determined the nucleotide sequence of 19 pig V, 12 J, and two D. Sequence comparisons identified 17 different V families and two J clusters homologous to the human J1 and J2. The fact that the pig J1 segments were always found joined to the D1-like sequence in numerous rearranged TCR cDNA suggests the existence of two D-J clusters in swine. These results also imply that the polymorphism of the porcine TCR segments is similar to that found in human. Finally, we report the discovery of a new and functional V subfamily named V100, which exhibited similarity to the murine V2 sequence but had no described V homolog in humans. Pilot spectratyping studies on V usage revealed a clonal dominance of V100⁺ T cell subsets among infiltrating cells in two accepted grafts.

This article has been cited by other articles:

				C. Baron, I. McMorrow, D. H Sachs, and C. LeGuern Persistence of Dominant T Cell Clones in Accepted Solid Organ Transplants J. Immunol., October 15, 2001; 167(8): 4154 - 4160. [Abstract] [Full Text] [PDF]