Original Article

An N-acetylated Natural Ligand of Human Histocompatibility Leukocyte Antigen (HLA)-B39: Classical Major Histocompatibility Complex Class I Proteins Bind Peptides with a Blocked NH₂ Terminus In Vivo

Correspondence to: José A. López de Castro, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Cantoblanco, 28049 Madrid, Spain. Tel:34-91-397-80-50 Fax:34-91-397-80-87 E-mail:aldecastro{at}cbm.uam.es.

Sequence-independent interactions involving the free peptidic NH₂ terminus are thought to be an essential feature of peptide binding to classical major histocompatibility complex (MHC) class I proteins. Challenging this paradigm, a natural N-acetylated ligand of human histocompatibility leukocyte antigen (HLA)-B39 was identified in this study. It matched the NH₂-terminal sequence of two human helicases, was resistant to aminopeptidase M, and was produced with high yield from a synthetic 30 mer with the sequence of the putative parental protein by the 20S proteasome. This is the first reported natural ligand of classical MHC class I antigens that has a blocked NH₂ terminus.

Key Words: human, antigen processing, biochemistry, molecular biology, tolerance

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This article has been cited by other articles:

• Marcilla, M., Cragnolini, J. J., Lopez de Castro, J. A. (2007). Proteasome-independent HLA-B27 Ligands Arise Mainly from Small Basic Proteins. Mol. Cell. Proteomics 6: 923-938 [Abstract] [Full Text]  
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