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

  • Edward J. Collins


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.


Major Histocompatibility Complex Class Peptide Binding Major Histocompatibility Complex Molecule Solvent Accessible Surface Area Histocompatibility Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  • Edward J. Collins

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