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Comment
. 2005 Jun 14;102(24):8399-400.
doi: 10.1073/pnas.0503313102. Epub 2005 Jun 6.

Bird genes give new insights into the origins of lipid antigen presentation

Steven A Porcelli  1
Affiliations
Comment

Bird genes give new insights into the origins of lipid antigen presentation

Steven A Porcelli. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Fig. 1.
Fig. 1.
CD1 structure and evolution. (A) Schematic views of the three separate families of antigen-presenting molecules and their mechanisms of antigen binding. MHC class I and CD1 molecules have three extracellular domains of similar size (α1, α2, and α3), and both bind β2-microglobulin. MHC class II has a similar overall domain arrangement but is a heterodimer of two transmembrane polypeptide chains (α and β). Both MHC class I and II have relatively shallow peptide-binding grooves at their membrane distal ends. For MHC class I, both ends of the bound peptides are usually contained within the groove, limiting the peptide length to 8–10 aa. In contrast, MHC class II can bind much longer peptides that protrude from the open ends of its groove. The CD1 groove is larger, deeper, and much more hydrophobic. It binds the hydrophobic alkyl tails of lipids, anchoring the ligand so that its more hydrophilic portions are exposed at the groove entrance. In all three cases, ligand binding to these molecules generates stable complexes that are recognized by the antigen receptors on specific T lymphocytes. (B) Simplified phylogenetic tree illustrating evolution of MHC and CD1. A “primordial MHC” locus that lacks MHC class I and II and CD1 genes has been described in the protochordate amphioxus, and a similar locus is proposed to exist in primitive jawless fish (i.e., lamprey, hagfish). The MHC-encoded peptide antigen-presenting systems most likely emerged with the acquisition of adaptive immunity, thought to have occurred ≈500 million years ago with the introduction of the recombinase activating genes into the vertebrate genome, leading to the ability to create large numbers of T and B cell antigen receptors through somatic recombination. The presence of both MHC class I and II genes in the cartilaginous fish (sharks) and their apparent absence in the jawless fish is consistent with this scheme. The new reports of CD1 in birds now allow the conclusion that this antigen-presenting system dates back at least to the emergence of the last common ancestor of birds and mammals (≈310 million years ago, illustrated as the red portion of the tree). The question marks in the red arrow indicate the remaining uncertainty about whether CD1 may have originated even earlier, possibly at about the same time as or even before MHC class I and II.
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