Evidence indicating independent assortment of framework and complementarity-determining segments of the variable regions of rabbit light chains. Delineation of a possible J minigene.

Abstract

The variable (V) 1 regions of immunoglobulin light chains when aligned for maximum homology can be divided into four framework regions (FR) separated by three complementarity-determining (CDR) (hypervariable [1]) regions or segments (2, 3). The latter as predicted (1), together with the corresponding three CDR of the heavy chain (4), form the antibody-combining sites (3-11). Light chains FR1, FR2, FR3, and FR4 comprise residues 1-23, [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][98][99][100][101][102][103][104][105][106][107] CDR2,[50][51][52][53][54][55][56][89][90][91][92][93][94][95][96][97]. If the FR segments were grouped into sets of identical sequence and the members of each set were traced, it was shown (12) that members of a given FRI set could be associated with different FR2, FR3, and FR4 sets. This independent assortment suggested that the FR sets, and by implication the CDR sets, were under different genetic control, and the hypothesis was put forward that the individual FR and CDR sets were controlled by minigenes assembled somatically by recombination at the DNA level (12). A minigene is defined as a segment of DNA coding for a portion of a domain and which shows evidence of segregation as a functional unit independent of the rest of the DNA coding for the V region (13). Because we only assorted FR segments, the findings would be independent of whether one or two residues of a given CDR assorted with any FR segment. Studies by Tonegawa et al. with cloned mouse Vx (14, 15) and V~ (16) genes and by Seidman et al. (17,18) with mouse V, genes showed that in 12-d-old embryo DNA, genes

Antigen‐specific blocking of CD4‐Specific immunological synapse formation using BPI and current therapies for autoimmune diseases

“…42 The variable domain has the greatest diversity as a complementary-determining region 3 (CDR3). 43 The sequence of CDR3 is primarily involved in recognizing the antigenic peptide presented by MHC molecules on APC. 44 MHC class I and class II molecules on APC bind observed at 24-48 hr after priming, 87 and the strength of expression correlates with stimulus by TCR 88 upon recruiting Src homology 2 (SH2) domain-containing phosphatase-2 (SHP-2) during T-cell activation.…”

Evidence for the Murine IgH μ Locus Acting as a Hot Spot for Intrachromosomal Homologous Recombination

“…In somatic cells, an ever-increasing body of evidence supports an important role for homologous recombination in remodelling of the chromosomal Ig genes. Gene conversion is important in generating Ab diversity in birds and rabbits (10,11), and may also play a role in the diversification of some mammalian Ab responses (12)(13)(14)(15)(16)(17)(18)(19)(20). Both gene conversion and crossing over occur between Ig H chain constant segments within regions of shared homology (21)(22)(23)(24).…”

Antibody Diversity: Something for Everyone

“…On the other hand, there are nowhere near the 20,000 genes advocated by early proponents of the germ-line theory [6]. In addition, recent discoveries at both the DNA [13] and protein [21] level indicate the importance of V-region gene interactions in the generation of diversity, and there is even some evidence to suggest that 'hypervariable insertion' may occur [7,17].…”