Andrew J. MURPHY,Lynn MACDONALD,Cagan GURER,Christos KYRATSOUS
申请号：
MX2017012829
公开号：
MX2017012829A
申请日:
2016.04.06
申请国别(地区):
MX
年份:
2018
代理人:
摘要：
Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and/or CD8 (e.g., CD8a and/or CD8ß )), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and/or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II a and/or MHC II ß chains) and/or MHC I (e.g., MHC I a ) respectively, and optionally human or humanized ß2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and/or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and/or MHC I, respectively) and/or the humanized TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.En la presente descripción se describen animales no humanos (por ejemplo, roedores, por ejemplo, ratones o ratas) genéticamente modificados para expresar un correceptor de células T humanizado (por ejemplo, CD4 y/o CD8 humanizado (por ejemplo, CD8a y/o CD8ß), un receptor de célula T (TCR) humano o humanizado que comprende un dominio variable codificado mediante al menos un segmento de gen de región variable del TCR humano y/o un complejo mayor de histocompatibilidad que se une al correceptor de célula T humanizado (por ejemplo, MHC II humano o humanizado (por ejemplo, cadenas del MHC II a y/o MHC II ß) y/o MHC I (por ejemplo, MHC Ia) respectivamente, y opcionalmente, microglobulina ß2 humana o humanizada). Se proporcionan, además, los embriones, tejidos, y células que los expresan. Se proporcionan, además, métodos para crear un
