High impact information on Lphn2

• To study the effects of altered carbohydrate structure on Ab effector function, we have used gene transfection techniques to produce mouse-human chimeric IgG1 Abs in the Chinese hamster ovary (CHO) cell line Lec 1, which is incapable of processing the high-mannose intermediate through the terminal glycosylation steps [1].
• The altered carbohydrates expressed at the surface of Lec9 cells appeared to be responsible for their loss of tumorigenicity, because revertants for lectin resistance were able to form tumors, and a double mutant (Lec9.Lec1) that expressed a Lec1 glycosylation phenotype also formed tumors [2].
• We had previously shown that IgG1 Abs produced in the cell line Lec 1, which attaches a high-mannose intermediate carbohydrate, were severely deficient in complement activation, showed a slightly reduced affinity for Fc gammaRI, and had a reduced in vivo half-life [3].
• Comparison of GnTI sequences detected three mutations within the luminal domain of Lec1 GnTI, each resulting in an amino acid substitution [4].
• Glycosylation defect in Lec1 Chinese hamster ovary mutant is due to a point mutation in N-acetylglucosaminyltransferase I gene [4].

Anatomical context of Lphn2

• We also produced IgG1 Abs in Pro-5, the wild-type CHO cell line that is the parent of Lec 1 [1].
• Both Lec1 GnTI and the GnTI mutant (Cys123 --> Arg123) are correctly localized to the Golgi apparatus, indicating that the inactive GnTI molecules are sufficiently well folded for efficient transport from the endoplasmic reticulum [4].

Associations of Lphn2 with chemical compounds

• Analysis of the attached carbohydrates shows those present on IgG1-Lec 1 were mannose terminated [5].

Other interactions of Lphn2

• We have now produced mouse-human chimeric IgG1 in wild-type Chinese hamster ovary (CHO) cell lines Pro-5 as well as in the glycosylation mutants Lec 2, Lec 8, and Lec 1 [5].

References