Functional consequences of TCR transgenic β-chain expression (TUM2P.908)

Abstract

Abstract We have generated mouse strain expressing transgenic β-chain of TCR 1D1 (belonging to the Vβ6 family) on the genetic background B10.D2(R101) (KdIdDb). The repertoire of peripheral T lymphocytes in these mice contains 70-80% of T cells expressing transgenic β-chain and 20-30% of T cells expressing endogenous β-chains. Expression of transgenic β-chain resulted in T cells with phenotype CD44-CD62L+ characteristic of “naïve” T lymphocytes. On the contrary, CD8+ T lymphocytes expressing endogenous β-chains had surface phenotype of activated effectors CD44+CD62L-. In wild-type B10.D2(R101) mice, immunization with lymphoma EL4 (H-2b) cells induced a vigorous CTL response targeted to the H-2Kb molecule and resulted in full rejection of the tumor cells. In contrast, transgenic mice developed a compromised proliferative response in MLR and were unable to reject transplanted allogeneic EL4 cells. During the immune response to EL4 cells, mostly CD8+ T-lymphocytes with endogenous β-chains became CD44+CD62L- effectors in transgenic mice, whereas only a small part of the T-lymphocytes expressing transgenic β-chains became effectors. Effectors CD8+CD44+CD62L- expressing endogenous β-chains showed enhanced expression of PD-1 and contained increased percent of KLRG1-positive cells. The acquisition of these characteristic features was associated with immune selection of H-2Kb-negative EL4 cells and subsequent tumor escape.