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“…This observation may indicate that not all H-and L-chain associations are comparable, and that some combinations may be fitter in chain pairing, rate of assembly, or stability. Experimental measurements of H͞L association are consistent with this possibility (40). On the other hand, it is unclear whether such selectivity is a general phenomenon because the 3-83KI genes may be underexpressed relative to their normal and conventional transgenic counterparts owing to the truncation of their 5Ј sequences in the targeting constructs, such that two gene copies are now required to compensate for this artificially lowered expression.…”
Section: Discussionmentioning
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“…This observation may indicate that not all H-and L-chain associations are comparable, and that some combinations may be fitter in chain pairing, rate of assembly, or stability. Experimental measurements of H͞L association are consistent with this possibility (40). On the other hand, it is unclear whether such selectivity is a general phenomenon because the 3-83KI genes may be underexpressed relative to their normal and conventional transgenic counterparts owing to the truncation of their 5Ј sequences in the targeting constructs, such that two gene copies are now required to compensate for this artificially lowered expression.…”
Section: Discussionmentioning
“…The H103-3 location at the C-terminal part of the recombination region between D and J H mini-gene products (still in HCDR3) makes it susceptible to alterations by nucleotide insertions and deletions (Tonegawa, 1983). Together, these observations suggest that somatic diversification of HCDR3 can fulfil preponderant roles in the alteration of both VH-VL association and recognition properties of antibody repertoires (Hamel et al, 1984;Stevens et al, 1988;Pokkuluri et al, 1998).…”
Section: Residues With High Contact Percentage At the Interfacementioning
“…3A). Moreover, during normal Ig assembly, an initial non-covalent V L -V H interaction is a prerequisite for the formation of the HC-LC interchain disulfide bond (Percy et al 1975; Secher et al 1977; Hamel et al 1984; Chothia et al 1985; Hamel et al 1987). To determine whether a similar V L -V H interaction was required to initiate the formation of λ 2 in the presence of C128S, we used the F62S mutant of λ.…”
Section: Resultsmentioning
“…In addition, two types of interchain disulfide bonds stabilize the tetrameric structure of functional Igs; one that links two HC to each other and another that bridges each HC to LC (Edelman and Gall 1969). Assembly of LCs and HCs is initiated by non-covalent interactions between their respective V L and V H variable regions (Percy et al 1975; Secher et al 1977; Hamel et al 1984; Chothia et al 1985; Hamel et al 1987). This is followed by hydrophobic interaction between C L and C H 1, the constant domains of LC and HC, respectively (Janeway 1994), which is eventually stabilized by a covalent interchain disulfide between these two constant domains (Hamel et al 1987; Hendershot et al 1987; Leitzgen et al 1997).…”
Section: Introductionmentioning