A SYNTHETIC RANDOM BASIC COPOLYMER WITH PROMISCUOUS BINDING TO CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES INHIBITS T-CELL PROLIFERATIVE RESPONSES TO MAJOR AND MINOR HISTOCOMPATIBILITY ANTIGENS IN-VITRO AND CONFERS THE CAPACITY TO PREVENT MURINE GRAFT-VERSUS-HOST DISEASEIN-VIVO

Graft-versus-host disease (GVHD) is a T-cell-mediated disease of trans planted donor T cells recognizing host alloantigens, Data presented in this report show, to our knowledge, for the first time that a synthet ic copolymer of the amino acids L-Glu, L-Lys, L-Ala, and L-Tyr (molecu lar ratio, 1.9:6.0:4.7:1.0; M(r), 6000-85000), termed GLAT, with promi scuous binding to multiple major histocompatibility complex class II a lleles is capable of preventing lethal GVHD in the B10.D2 --> BALB/c m odel (both H-2(d)) across minor histocompatibility barriers, Administr ation of GLAT over a limited time after transplant significantly reduc ed the incidence, onset, and severity of disease, GLAT also improved l ong-term survival from lethal GVHD: 14/25 (56%) of experimental mice s urvived > 140 days after transplant compared to 2/26 of saline-treated or to 1/10 of hen egg lysozyme-treated control mice (P < 0.01), Long- term survivors were documented to be fully chimeric by PCR analysis of a polymorphic microsatellite region in the interleukin 1 beta gene, I n vitro, GLAT inhibited the mixed lymphocyte culture in a dose-depende nt fashion across a variety of major barriers tested, Furthermore, GLA T inhibited the response of nylon wool-enriched T cells to syngeneic a ntigen-presenting cells presenting minor histocompatibility antigens, Prepulsing of the antigen-presenting cells with GLAT reduced the proli ferative response, suggesting that GLAT inhibits antigen presentation.