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Crystallographic Analysis of Peptide Binding by Class I and Class II Major Histocompatibility Antigens

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MHC Molecules: Expression, Assembly and Function

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Abstract

Crystallographic structures can be thought of as snapshots of molecules in action. A book of such structural snapshots would yield a “field guide” that contributed important information about the mechanisms of enzyme action, DNA control or immunological recognition. This contribution is perhaps best highlighted by the structure of the human class I molecule, HLA-A2, which resulted in the rethinking of the process of MHC restriction and T cell recognition.1 Prior to the structure, one popular model of MHC restriction suggested that viral proteins existed on the surface of cells adjacent to the class I molecule and were thus recognized jointly by T cells. However, the crystallographic solution (or snapshot) of the structure of HLA-A2.1 showed a large cleft in the surface of the protein that appeared to bind short peptides. This, taken with the evidence that soluble viral peptides could stimulate T cells2,3 was interpreted to mean that histocompatibility molecules present small peptides to T cells.1,4 Additional snapshots now seek to understand how these molecules bind diverse sets of peptides with nanomolar dissociation constants and half-lives measured in days.

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  1. Edward J. Collins
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Collins, E.J. (1996). Crystallographic Analysis of Peptide Binding by Class I and Class II Major Histocompatibility Antigens. In: MHC Molecules: Expression, Assembly and Function. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-6462-7_8

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  • DOI: https://doi.org/10.1007/978-1-4684-6462-7_8

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