Recent studies have revealed the expression of multiple putative cytoplasmic dynein heavy chain (DHC) genes in several organisms, with each gene encoding a separate protein isoform. This finding is consistent with the hypothesis that different isoforms do different things, as is the case for the axonemal dyneins. Furthermore, the large number of tasks ascribed to cytoplasmic dynein suggests tha...

OBJECTIVES AND DESIGN Developing an effective HIV-1 vaccine that elicits broadly neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive studies on HIV-1 have revealed various strategies employed by the virus to escape host immune surveillance. Here, we investigated the human antibody gene repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA) a...

Antibody repertoires are known to be shaped by selection for antigen binding. Unexpectedly, we now show that selection also acts on a non-antigen-binding antibody region: the heavy-chain variable (VH)-encoded "elbow" between variable and constant domains. By sequencing 2.8 million recombined heavy-chain genes from immature and mature B-cell subsets in mice, we demonstrate a striking gradient in...

Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repe...

The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an e...

The variable regions of five human immunoglobulin heavy chains of the V(H)III subgroup have been totally sequenced. Three of the heavy chains belonged to the IgG class and two to the IgA class. Examination of these sequences, and comparison with additional published heavy chain sequences, showed that a total of four hypervariable regions is characteristic of human heavy chain variable regions. ...

The anti-DNP antibodies produced by primary and secondary splenic foci were analyzed for heavy chain class by a radioimmunoassay, using iodinated, purified goat antimouse micro-chain antibody and goat antimouse gamma1 chain antibody. The frequency of primary and secondary foci producing both IgM and IgG1 anti-DNP antibody (16% and 14%, respectively) was considerably higher than that which would...

759 he discovery of immunoglob-ulin heavy chain binding protein (BiP) in antibody-producing cells (Morrison and Scharff, 1975; Haas and Wabl, 1984) had researchers trying to assign an immune function to it. In one theory, BiP was thought to regulate allelic exclusion of heavy and light chain genes (Wabl and Steinberg, 1982). Part of the theory assumed that BiP neutralized a proposed heavy chain...