Lectture 10 Biol302 Spring.ppt

Lectture 10 Biol302 Spring 2012The Differentiation of Vertebrate Immune Cells ?In the immune system, two types of cells participate directly in defense against pathogens. ?Plasma B cells produce and secrete immunoglobulins (antibodies), and killer T cell produce membrane- bound proteins that act as receptors for various substances. ?B cell antibodies and T cell receptors bind to specific antigens. A cell must make many varieties of these proteins because there are many potential pathogens. An Antigen-plex Structure of an Antibody Molecule Human Antibody Genes ?Two light chain loci: the ? on chromosome 2 and ? on chromosome 22 ?One heavy chain locus on chromosome 14. ?Each locus consists of a long array of gene segments. Gene Segments for a Kappa Polypeptide ?An L ? V? gene segment, encoding a leader peptide, which is removed later, and the N-terminal 95 amino acids of the variable region of the kappa light chain. (76 gene segments in humans; 40 of these are functional) ?A J ? gene segment, encoding the last 13 amino acids of the variable region of the kappa light chain. (5 gene segments in humans) ?A C ? gene segment, encoding the constant region of the kappa light chain. (1 gene segment in humans) The Kappa Locus ?During B cell development, the kappa light chain gene that will be expressed is assembled from one L? V? segment, one J ? segment, and the C ? segment by somatic bination. ?Segment joining is mediated by bination signal sequences adjacent to each gene segment by a plex including RAG1 and RAG2 (bination activating gene proteins 1 and 2). Many Different Antibodies Can Be Produced ?40 L ? V? segments ? 5 J ? segments ? 1 C ? segment = 200 kappa light chains. ?bination of gene segments can create 120 lambda light chains and 6600 different heavy chains. ?Combinatorial assembly of these allows production of 2,112,000 different antibodies. ?Even more antibodies are possible due to variation in bination sites and hypermutability of the var