Cytotoxic T lymphocyte recognition of a xenogeneic major histocompatibility complex antigen expressed in transgenic mice

Abstract

Introduction of a porcine major histocompatability complex (MHC) class I gene (PD1) into the genome of a C57BL/10 (B10) mouse has been shown to lead to cell surface expression of the porcine MHC antigen, SLAPD1 in a transgenic mouse. The PD1 product expressed on spleen cells from the transgenic mice stimulated B10 spleen cells in a mixed lymphocyte culture to generate PD1-specific cytotoxic T lymphocytes (CTL). The CTL were PD1 specific since they lysed transgenic splenic blast cells and PD1-transfected L cells, but not B10 blasts or control L cells. The CTL were L3T4-, Lyt-2+ and their activity was partially inhibited by either anti-Lyt-2 antibody or by anti-swine MHC alloantibodies. The repertoire of responding B10 anti-transgenic CTL was assessed by examining their cross-reactivity on a series of murine allogeneic targets. The B10 anti-transgenic CTL showed some cross-reactivity on conventional allogeneic targets, but reacted strongly on a series of mutant H-2Kbm blast cells. In addition, B10 anti-B6.cH-2bm6 CTL cross-reacted extensively on the transgenic target cells. These results demonstrated that normal B10 CTL possess a repertoire specific for the products of the xenogeneic class I gene PD1, that this repertoire is cross-reactive with the conventional alloreactive CTL repertoire, and that there exists an unanticipated relationship between PD1-specific CTL and CTL specific for Kb mutant determinants.