Major Histocompatibility Complex Class I: Difference between revisions
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In 1987, Bjorkman and coworkers (in the laboratory of Don Wiley at Harvard) published the first empirical structure of MHC, a crystallographic structure of the human MHC Class I protein HLA-A2 ([[1hla]]). Although the resolution was low (3.5 Å), there was sufficient information to explain the decade-long mystery of how MHC restricts the recognition of foreign antigens by T lymphocytes. It is difficult to exaggerate the impact that this structure, and those that followed, had on the field of immunology. | In 1987, Bjorkman and coworkers (in the laboratory of Don Wiley at Harvard) published the first empirical structure of MHC, a crystallographic structure of the human MHC Class I protein HLA-A2 ([[1hla]]). Although the resolution was low (3.5 Å), there was sufficient information to explain the decade-long mystery of how MHC restricts the recognition of foreign antigens by T lymphocytes. It is difficult to exaggerate the impact that this structure, and those that followed, had on the field of immunology. | ||
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[[Image:1hla_edm_fig6b.jpg|340 px]] | |||
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<font color='blue'>Electron density of HLA-A2 peptide-binding groove</font> showing <font color='#ca4e61'>density of mixed peptides</font>. Figure 6b from [[1hla#Reference | Bjorkman <i>et al., Nature</i> <b>329</b>:506]], used with permission of Dr. Pamela Bjorkman. | |||
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Wiley's team struggled for many years to obtain sufficient MHC protein and high quality crystals. During this struggle, their funding ran out but they persevered, using funds from other projects (personal communication to [[User:Eric Martz |Eric Martz]] from Wiley, ca. 1989). The MHC protein was obtained from cultures of human cells (the JY B lymphocyte cell line) by a well-established but arduous process that earlier had been used for obtaining the amino acid sequences of HLA proteins by Strominger and coworkers. Papain was used to cleave the soluble extracellular domains of the HLA MHC proteins from their transmembrane domains, and the HLA-A2 domains were purified, separating them from HLA-B7 among many other proteins present on these cells. | Wiley's team struggled for many years to obtain sufficient MHC protein and high quality crystals. During this struggle, their funding ran out but they persevered, using funds from other projects (personal communication to [[User:Eric Martz |Eric Martz]] from Wiley, ca. 1989). The MHC protein was obtained from cultures of human cells (the JY B lymphocyte cell line) by a well-established but arduous process that earlier had been used for obtaining the amino acid sequences of HLA proteins by Strominger and coworkers. Papain was used to cleave the soluble extracellular domains of the HLA MHC proteins from their transmembrane domains, and the HLA-A2 domains were purified, separating them from HLA-B7 among many other proteins present on these cells. | ||
Because the protein was obtained from living cells, its '''<font color='blue'>peptide-accomodating groove (blue in figure at right)</font>''' contained a '''<font color='#ca4e61'>mixture of unknown peptides (salmon-colored in figure at right)</font>'''. These appeared in the crystal structure of [[1hla]] as an electron density that could not be explained by the known sequence of HLA-A2, lying within a groove the alpha chain of that molecule, in their Fig. 6b (at right). This phenomenally enlightening preview of ghostly peptides being presented to T cells by MHC gave goosebumps to cellular immunologists of the time. | Because the protein was obtained from living cells, its '''<font color='blue'>peptide-accomodating groove (blue in figure at right)</font>''' contained a '''<font color='#ca4e61'>mixture of unknown peptides (salmon-colored in figure at right)</font>'''. These appeared in the crystal structure of [[1hla]] as an electron density that could not be explained by the known sequence of HLA-A2, lying within a groove the alpha chain of that molecule, in their Fig. 6b (at right). This phenomenally enlightening preview of ghostly peptides being presented to T cells by MHC gave goosebumps to cellular immunologists of the time. | ||
==MHC Structure Tutorial== | ==MHC Structure Tutorial== | ||
