Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005.

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Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Genomic organization of the antigen receptor loci in human beings Genomic organization of the antigen receptor loci in human beings. The maroon, green, purple and blue rectangles represent V, D, J and C segments, respectively and the blue ovals indicate enhancers. (a) The human IgH locus, located on chromosome 14 at band 14q32.33. It has 123 to 129 IgHV genes depending on haplotypes, 27 IgHD segments, and nine IgHJ segments and in the most frequent haplotype, 11 IgHC genes. (b) The human IgK locus located on the chromosome 2, at band 2p11.2. It consists of 76 IgKV genes, five IgKJ segments, and a unique IgKC gene. (c) The human IgL locus located on chromosome 22 at band 22q11.2. It consists of 73 to 74 IgLV genes, 7 to 11 IgLJ and 7 to 11 IgLC genes depending on the haplotypes. (d) The human TCRA locus located on chromosome 14 at band 14q11.2. It consists of 116 genes: 54 TCRAV, 61 TCRAJ and a unique TCRAC gene. TCRD locus is embedded in the TCRA locus, between the TCRAV and TCRAJ genes. Though represented in the figure as ‘TCRAV 54’, among the 54 V genes, five can be rearranged to either TCRAJ or TCRDD genes and therefore can be used in the synthesis of α or δ chains. (e) The human TCRB locus on chromosome 7 at 7q34, consisting of 64–67 TCRBV, 2 TCRBD, 14 TCRBJ and two TCRBC genes. (f) The human TCRG locus is on chromosome 7 at 7p14 and consists of 12–15 TCRGV, five TCRGJ and two TCRGC1 genes. The data presented are in accordance with IMGT (http://www.imgt.org). IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Immunology Volume 137, Issue 4, pages 271-281, 20 NOV 2012 DOI: 10.1111/imm.12009 http://onlinelibrary.wiley.com/doi/10.1111/imm.12009/full#imm12009-fig-0001

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Mechanism of the V(D)J recombination. (a) Mechanism of the V(D)J recombination. (a). Recombination Signal Sequence (RSS). In 12RSS (represented by open triangle), the heptamer is separated from nonamer by 12 bp and in 23RSS (represented by closed triangle) by 23 bp. (b). Distribution of RSS at the seven antigen receptor loci in human beings and the 12/23 rule. The V, D and J regions of the coding segments are depicted as rectangles; the flanking 12RSS is represented by an open triangle and 23RSS by a closed triangle. As per the ‘12/23 rule’, V(D)J recombination is restricted to gene segments that are flanked by signals of different spacer lengths. (c). Mechanism of V(D)J recombination. Schematic model of the protein–DNA complexes in V(D)J recombination. The 12RSS and 23RSS are represented as white and blue triangles, respectively. Coding segments are shown as rectangles and proteins as shaded ovals. ‘V’ stands for variable and ‘J’ for joining gene segments. Recombination activating genes (RAGs; shaded ovals) bind the RSS and introduce a single‐strand nick in the DNA precisely at the border between the heptamer of RSS and the coding segment. This nick generates a free 3′‐OH group on the coding end which is then covalently linked to the opposing phosphodiester bond, leaving a covalently closed hairpin on the coding end and a blunt 5′ phosphorylated signal end. The ends remain associated with RAGs; constituting a transitory structure referred to as ‘post‐cleavage complex’. Following this, the coding ends are processed and joined by NHEJ to create the exon, which forms the antigen‐binding region of antigen receptors. Signal end remains bound to RAGs constituting a ‘signal end complex’ that forms the signal joint. IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Immunology Volume 137, Issue 4, pages 271-281, 20 NOV 2012 DOI: 10.1111/imm.12009 http://onlinelibrary.wiley.com/doi/10.1111/imm.12009/full#imm12009-fig-0002

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

Pierce, GENETICA, Zanichelli editore S.p.A. Copyright © 2005

HLA polymorphism Figure by Thomas Blicher (blicher@cbs.dtu.dk

HLA polymorphism