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CD4 is a cell surface glycoprotein that acts as a co-receptor for the T cell antigen receptor by binding to a non-polymorphic portio n of MHC molecules. CD4 also functions as a receptor for human immuno-deficiency virus type-I (HIV-1) because the viral envelope glycoprotein gp120 binds to CD4 with a high affinity. We have previously demonstrated that introduction of mutations into CD4 abolished the binding of gp120 and prevented HIV-1 from entering cells and spreading. How ever, whether introduction binding to MHC and loss of function is yet to be determined. We generated transgenic mouse lines by injecting a mutant human CD4 (muthCD4) gene under a murine CD4 enhancer/promoter to ensure tissue and stage specific expression. To exclude the influence of endogenous murine CD4, transgenic mice were crossed with murine CD4-targeted mice to produce muthCD4 transgenic mice lacking endo-genous CD4 (muthCD4TG/KO mice). In these mice, T lymphocytes expressing muthCD4 expanded and matured in the thymus and were present in the spleen and lymph nodes. They also activated B cells to mount an antibody response to a T-dependent antigen. The results from this study suggest that a human variant of CD4 modified to be resistant to HIV-1 ment in the thymus in vivo , having helper T cell functions. Thus, further characterization of muthCD4 molecules should open the way to new HIV treatment modalities.
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참고문헌 (20)
참고문헌 신청
Biddison WE / jexpmed1982;156 / Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigen : 1065 ~ 76
Clayton LK / nature1989;339 / Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding : 548 ~ 51
Coffin JM / 1995 / HIV population dynamics in vivo: implication for genetic variation, pathogenesis, and therapy 267 : 483 ~ 489
Fleury S / / Mutational analysis of the interaction between CD4 and class II MHC : 1037 ~ 49
Kehrli L / / the transfer of Tat-inducible interferon genes protects human cells against HIV-1 challenge in vitro and in vivo in severe combined mariglia (m)
Clayton LK / nature1989;339 / Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding : 548 ~ 51
Coffin JM / 1995 / HIV population dynamics in vivo: implication for genetic variation, pathogenesis, and therapy 267 : 483 ~ 489
Fleury S / / Mutational analysis of the interaction between CD4 and class II MHC : 1037 ~ 49
Kehrli L / / the transfer of Tat-inducible interferon genes protects human cells against HIV-1 challenge in vitro and in vivo in severe combined mariglia (m)
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